1.Recurrent pulmonary infection and oral mucosal ulcer.
Fei-Mei KUANG ; Lan-Lan TANG ; Hui ZHANG ; Min XIE ; Ming-Hua YANG ; Liang-Chun YANG ; Yan YU ; Li-Zhi CAO
Chinese Journal of Contemporary Pediatrics 2017;19(4):452-457
		                        		
		                        			
		                        			An 8-year-old girl who had experienced intermittent cough and fever over a 3 year period, was admitted after experiencing a recurrence for one month. One year ago the patient experienced a recurrent oral mucosal ulcer. Physical examination showed vitiligo in the skin of the upper right back. Routine blood tests and immune function tests performed in other hospitals had shown normal results. Multiple lung CT scans showed pulmonary infection. The patient had recurrent fever and cough and persistent presence of some lesions after anti-infective therapy. The antitubercular therapy was ineffective. Routine blood tests after admission showed agranulocytosis. Gene detection was performed and she was diagnosed with dyskeratosis congenita caused by homozygous mutation in RTEL1. Patients with dyskeratosis congenita with RTEL1 gene mutation tend to develop pulmonary complications. Since RTEL1 gene sequence is highly variable with many mutation sites and patterns and can be inherited via autosomal dominant or recessive inheritance, this disease often has various clinical manifestations, which may lead to missed diagnosis or misdiagnosis. For children with unexplained recurrent pulmonary infection, examinations of the oral cavity, skin, and nails and toes should be taken and routine blood tests should be performed to exclude dyskeratosis congenita. There are no specific therapies for dyskeratosis congenita at present, and when bone marrow failure and pulmonary failure occur, hematopoietic stem cell transplantation and lung transplantation are the only therapies. Androgen and its derivatives are effective in some patients. Drugs targeting the telomere may be promising for patients with dyskeratosis congenita.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Dyskeratosis Congenita
		                        			;
		                        		
		                        			complications
		                        			;
		                        		
		                        			therapy
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Mouth Diseases
		                        			;
		                        		
		                        			etiology
		                        			;
		                        		
		                        			Mouth Mucosa
		                        			;
		                        		
		                        			pathology
		                        			;
		                        		
		                        			Recurrence
		                        			;
		                        		
		                        			Respiratory Tract Infections
		                        			;
		                        		
		                        			etiology
		                        			;
		                        		
		                        			Telomere
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Ulcer
		                        			;
		                        		
		                        			etiology
		                        			
		                        		
		                        	
2.Changes of miRNA after oral submucous fibrosis co-cultured with Salvia and low-dose prednisolone.
Binjie LIU ; Jun CHEN ; Xinchun JIAN
Journal of Central South University(Medical Sciences) 2014;39(5):471-476
		                        		
		                        			OBJECTIVE:
		                        			To explore and analyze the the expression change of miRNA associated with oral submucous fibrosis (OSF) treated by the Salvia combined with law-dose prednisolone.
		                        		
		                        			METHODS:
		                        			Ten pairs of tissues from patients with typical early or advanced stage clinical pathological features of OSF and their paired normal tissues (internal control), were selected respectively. The miRNA expression profiles between the OSF and its paired controls were compared by the Affymetrix analysis. The primary normal oral mucous cells were cultured in arecoline (50 μg/mL) for 3, 6, 12 d (0 d ser ved as cont rol), and the primary OSF-fibroblast cells were cultured with Salvia (90 mg/mL) combined with low-dose prednisolone for 12, 24, 36 h (0 h served as control). The differential expression of miRNA was detected.
		                        		
		                        			RESULTS:
		                        			Arecoline induced the expression changes of miRNAs in normal mucosal cells. Salvia combined with low doses of prednisolone reversed the related miRNA expression.
		                        		
		                        			CONCLUSION
		                        			MiRNAs play an essential role in the occurrence and development of OSF. Salvia combined with low-dose prednisolone can reverse the expression of related miRNAs in OSF cells.
		                        		
		                        		
		                        		
		                        			Arecoline
		                        			;
		                        		
		                        			Cells, Cultured
		                        			;
		                        		
		                        			Coculture Techniques
		                        			;
		                        		
		                        			Fibroblasts
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			MicroRNAs
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Mouth Mucosa
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Oral Submucous Fibrosis
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Prednisolone
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Salvia
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Transcriptome
		                        			
		                        		
		                        	
3.Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions.
Carol L FISCHER ; Katherine S WALTERS ; David R DRAKE ; Deborah V DAWSON ; Derek R BLANCHETTE ; Kim A BROGDEN ; Philip W WERTZ
International Journal of Oral Science 2013;5(3):130-140
		                        		
		                        			
		                        			Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria; however, little is known about their spectrum of antimicrobial activity or mechanisms of action against oral bacteria. In this study, we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Minimal inhibitory concentrations, minimal bactericidal concentrations, and kill kinetics revealed variable, but potent, activity of oral mucosal and salivary lipids against P. gingivalis, indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria, although specific components of bacterial membranes are also likely important. Electron micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma membrane. This information, coupled with the association of treatment lipids with P. gingivalis lipids revealed via thin layer chromatography, suggests that the plasma membrane is a likely target of lipid antibacterial activity. Utilizing a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique P. gingivalis stress response, including proteins important in fatty acid biosynthesis, metabolism and energy production, protein processing, cell adhesion and virulence. Prophylactic or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.
		                        		
		                        		
		                        		
		                        			Anti-Bacterial Agents
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Bacterial Proteins
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Colony Count, Microbial
		                        			;
		                        		
		                        			Fatty Acids
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lipids
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Microscopy, Electron
		                        			;
		                        		
		                        			Mouth Mucosa
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			microbiology
		                        			;
		                        		
		                        			Porphyromonas gingivalis
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			ultrastructure
		                        			;
		                        		
		                        			Saliva
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			microbiology
		                        			;
		                        		
		                        			Sphingolipids
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Virulence
		                        			;
		                        		
		                        			drug effects
		                        			
		                        		
		                        	
4.The similarity between human embryonic stem cell-derived epithelial cells and ameloblast-lineage cells.
Li-Wei ZHENG ; Logan LINTHICUM ; Pamela K DENBESTEN ; Yan ZHANG
International Journal of Oral Science 2013;5(1):1-6
		                        		
		                        			
		                        			This study aimed to compare epithelial cells derived from human embryonic stem cells (hESCs) to human ameloblast-lineage cells (ALCs), as a way to determine their potential use as a cell source for ameloblast regeneration. Induced by various concentrations of bone morphogenetic protein 4 (BMP4), retinoic acid (RA) and lithium chloride (LiCl) for 7 days, hESCs adopted cobble-stone epithelial phenotype (hESC-derived epithelial cells (ES-ECs)) and expressed cytokeratin 14. Compared with ALCs and oral epithelial cells (OE), ES-ECs expressed amelogenesis-associated genes similar to ALCs. ES-ECs were compared with human fetal skin epithelium, human fetal oral buccal mucosal epithelial cells and human ALCs for their expression pattern of cytokeratins as well. ALCs had relatively high expression levels of cytokeratin 76, which was also found to be upregulated in ES-ECs. Based on the present study, with the similarity of gene expression with ALCs, ES-ECs are a promising potential cell source for regeneration, which are not available in erupted human teeth for regeneration of enamel.
		                        		
		                        		
		                        		
		                        			Ameloblasts
		                        			;
		                        		
		                        			physiology
		                        			;
		                        		
		                        			Amelogenesis
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Amelogenin
		                        			;
		                        		
		                        			analysis
		                        			;
		                        		
		                        			Bone Morphogenetic Protein 4
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Cell Culture Techniques
		                        			;
		                        		
		                        			Cell Differentiation
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Cell Line
		                        			;
		                        		
		                        			Cell Lineage
		                        			;
		                        		
		                        			Embryonic Stem Cells
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			physiology
		                        			;
		                        		
		                        			Epithelial Cells
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			physiology
		                        			;
		                        		
		                        			Fibroblast Growth Factor 8
		                        			;
		                        		
		                        			analysis
		                        			;
		                        		
		                        			Hedgehog Proteins
		                        			;
		                        		
		                        			analysis
		                        			;
		                        		
		                        			Homeodomain Proteins
		                        			;
		                        		
		                        			analysis
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Keratins
		                        			;
		                        		
		                        			analysis
		                        			;
		                        		
		                        			classification
		                        			;
		                        		
		                        			Lithium Chloride
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			MSX1 Transcription Factor
		                        			;
		                        		
		                        			analysis
		                        			;
		                        		
		                        			Mouth Mucosa
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			Phenotype
		                        			;
		                        		
		                        			Regeneration
		                        			;
		                        		
		                        			physiology
		                        			;
		                        		
		                        			Skin
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			Transcription Factors
		                        			;
		                        		
		                        			analysis
		                        			;
		                        		
		                        			Tretinoin
		                        			;
		                        		
		                        			pharmacology
		                        			
		                        		
		                        	
5.Effects of dihydromyricetin on tumor necrosis factor and NF-kappaB p65 of RAU rats.
Xue-min YANG ; Xiao-hong WANG ; Li-feng CHEN ; Xiao-qing WANG
China Journal of Chinese Materia Medica 2012;37(17):2612-2617
OBJECTIVETo study the effects of dihydromyricetin (DMY) on tumor necrosis factor (TNF-alpha) and NF-kappaB p65 cells of the recurrent aphthous ulcer (RAU) rat.
METHODSixty of Sprague Dawley (SD) rats are randomly divided into 6 groups. The rat RAU models was established by injection of immunogen composed of the homogenate supernate of homogeneous oral mucosa from SD rats and Freund's complete adjuvant (FCA) into rat backs subcutaneously once every two weeks for 5 times, and the only FCA injected as normal control. DMY(50,100, 200 mg x kg(-1)) and licorzine (67.5 mg x kg(-1)) were given intragastrically once daily for 7 days on the day of the last immunogen injection, respectively. Water was given instead of drugs in normal and model control groups. The blood was got from the fundus oculi vein of rats on the day after last administration, the serum was separated. Then the rats were put to death with the cervical dislocation and decollated on the ice stage. Two sides of rat buccal mucosal tissue were cut. One side of them was put into 4% neutral formalin and another was added into 10 times of phosphate buffer to homogenize it homogenate. The oral mucosa ulcer occurrence of rats was observed by the histopathology. The content of TNF-alpha in serum and oral mucosa was assayed with ELISA; the expression of NF-kappaB cells was determined by the immunohistochemisty and macrophagus was determined by azure-feosin-dyeing in oral mucosa tissue. The expression of TNF-alpha mRNA in serum and oral mucosa was detected by reverse transcription polymerase chain reaction.
RESULTIn RAU rats, oral mucosa ulcer occurred, the content of TNF-alpha raised and the expression of TNF-alpha mRNA increased in serum and oral mucosa, the expression of positive NF-kappaB p65 cells and the amount of macrophages went up in oral mucosa. DMY and licorzine significantly reduced occurrence of oral mucosa ulcer in RAU rats, lowered content of TNF-alpha and the expression of TNF-alpha mRNA in serum and oral mucosa, reduced expression of positive NF-kappaB p65 cells and the amount of macrophages.
CONCLUSIONIt is considered that DMY could inhibited occurrence of oral mucosa ulcer in RAU rats. One principle of it's effects could be that DMY controlled NF-kappaB p65 regulation on transcription and release of TNF-alpha mRNA in macrophages in oral mucosa ulcer tissue and lead to fall of TNF-alpha content in oral mucosa tissue causing role of anti-oral mucosa ulcer.
Animals ; Disease Models, Animal ; Female ; Flavonols ; administration & dosage ; Humans ; Macrophages ; drug effects ; immunology ; Male ; Mouth Mucosa ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stomatitis, Aphthous ; drug therapy ; genetics ; immunology ; Transcription Factor RelA ; genetics ; immunology ; Tumor Necrosis Factor-alpha ; genetics ; immunology
6.Effects of Frozen Gauze with Normal Saline and Ice on Thirst and Oral Condition of Laparoscopic Cholecystectomy Patients: Pilot Study.
Eun A CHO ; Kye Ha KIM ; Jun Yeong PARK
Journal of Korean Academy of Nursing 2010;40(5):714-723
		                        		
		                        			
		                        			PURPOSE: The purpose of this study was to examine the effects of using gauze frozen with normal saline or ice on thirst-relief and oral condition of laparoscopic cholecystectomy patients. METHODS: A quasi-experimental nonequivalent control group, pretest-posttest design was used. Participants (n=53) received either gauze frozen with normal saline (n=17), ice (n=18) or wet gauze (n=18) for thirst-relief. The subjective thirst level and oral condition of the participants were assessed before the intervention, 15 min after the first intervention and 15 min after the second intervention. RESULTS: After oral care was provided twice, there were significant differences in thirst level among the groups. When oral care was provided twice, the oral condition of tongue, saliva, mucosal membrane, and gingiva was improved in patients receiving gauze frozen with normal saline or ice. CONCLUSION: Gauze frozen with normal saline and ice can be effective for oral care in reducing the thirst level and improving the condition of the oral cavity.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			*Cholecystectomy, Laparoscopic
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Freezing
		                        			;
		                        		
		                        			Gallbladder Diseases/*surgery
		                        			;
		                        		
		                        			Gingiva/drug effects
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			*Ice
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Mouth Mucosa/drug effects
		                        			;
		                        		
		                        			Pilot Projects
		                        			;
		                        		
		                        			Saline Solution, Hypertonic
		                        			;
		                        		
		                        			Saliva/physiology
		                        			;
		                        		
		                        			*Thirst/drug effects
		                        			;
		                        		
		                        			Tongue/drug effects
		                        			
		                        		
		                        	
7.Role of the Chinese herbal medicine xianhuayin on the reversal of premalignant mucosal lesions in the golden hamster buccal pouch.
Yan-zhi XU ; Yong-le QIU ; Zhi-guang AN ; Feng-ying YANG
International Journal of Oral Science 2010;2(1):53-58
AIMTo investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene (DMBA)-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters.
METHODOLOGYThe animals were randomly divided into a non-diseased control group (n=5) and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA (0.5% in acetone) to generate an oral mucosa premalignant lesion. Animals in the experimental group were further divided into Xianhuayin-treated group (n=30), untreated premalignant lesion group (n=10) and normal saline (NS)-treated group (n=10). The cheek (buccal) pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin.
RESULTSIn the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic (SEM) analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated-group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic microscopic (TEM) analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in NS-treated group and those in the untreated premalignant lesion group. Significant therapeutic efficacy was observed in the group receiving Xianhuayin.
CONCLUSIONXianhuayin is effective in the reversal of DMBA-induced premalignant lesions in the buccal pouch of golden hamsters.
9,10-Dimethyl-1,2-benzanthracene ; adverse effects ; Amomum ; Animals ; Anticarcinogenic Agents ; administration & dosage ; therapeutic use ; Carcinogens ; Carthamus tinctorius ; Cell Nucleus ; drug effects ; Cricetinae ; Desmosomes ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Epithelial Cells ; drug effects ; Epithelium ; drug effects ; Glycyrrhiza ; Hyperplasia ; Intercellular Junctions ; drug effects ; Intermediate Filaments ; drug effects ; Keratins ; Mesocricetus ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Mouth Mucosa ; drug effects ; pathology ; Mouth Neoplasms ; prevention & control ; Philodendron ; Poria ; Precancerous Conditions ; prevention & control ; Random Allocation ; Sodium Chloride
8.Inhibitory effect of baicalin on germ tube formation and adhesion of Candida albicans.
Changzhong WANG ; Xin FENG ; Xiaolu ZHANG ; Qian ZHU ; Chuanqi XIE ; Huijuan CHENG ; Yan WANG ; Yun YUN
China Journal of Chinese Materia Medica 2010;35(23):3216-3218
OBJECTIVETo investigate the effects of baicalin against Candida albicans germ tube formation, and adherence to buccal epitherial and vaginal epitherial cells.
METHODVarious concentrations of baicalin (100, 50, 10 mg x L(-1)) were incubated with C. albicans suspension, the mixed suspension of C. albicans and human buccal epitherial cells, the mixed suspension of C. albicans and vaginal epitherial cells, respectively. The effects of baicalin on C. albicans germ tube formation, and adherence to buccal epitherial and vaginal epitherial cells were then assessed microscopically.
RESULTAll concentrations of baicalin could inhibit C. albicans germ tube formation, and adherent to buccal epitherial and vaginal epitherial cells,while there was no significant difference between standard and clinical strains.
CONCLUSIONBaicalin could inhibit C. albicans germ tube formation, and adherence to buccal epitherial and vaginal epitherial cells.
Adult ; Anti-Infective Agents ; pharmacology ; Candida albicans ; drug effects ; growth & development ; physiology ; Candidiasis ; drug therapy ; microbiology ; Cheek ; microbiology ; Epithelial Cells ; microbiology ; Female ; Flavonoids ; pharmacology ; Humans ; Mouth Mucosa ; microbiology ; Vagina ; microbiology ; Young Adult
9.Regulation of calculus bovis on the function of mice oral fibroblasts.
Jianping DAI ; Jun CHEN ; Bangxing HAN ; Yufei BEI ; Xiaokun ZHOU
Chinese Journal of Biotechnology 2009;25(3):448-451
		                        		
		                        			
		                        			To explore the influence of calculus bovis on the function of primary cultured mice oral fibroblasts, we determined the effects of calculus bovis on the fibroblast proliferation, collagen production, matrix metalloproteinases-2, -9 activities and tissue inhibitor of metalloproteinase-1 production by MTT assay, chloramine T method, gelatin zymography and enzyme-linked immunosorbent assays respectively. The results showed that calculus bovis could significantly inhibit the proliferation of fibroblasts and collagen synthesis in a concentration dependent manner, could significantly (P<0.05) suppress matrix metalloproteinases-2 activity and very significantly (P<0.01) inhibit the production of tissue inhibitor of metalloproteinase-1. In conclusion, the major function of calculus bovis in the process of ulcer healing is not to promote tissue regeneration, the mechanism that calculus bovis inhibits collagen synthesis may be partly due to its ability to very significantly (P<0.01) suppress the production of tissue inhibitor of metalloproteinase-1.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Cattle
		                        			;
		                        		
		                        			Cell Proliferation
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Cells, Cultured
		                        			;
		                        		
		                        			Cholelithiasis
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			veterinary
		                        			;
		                        		
		                        			Collagen
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Fibroblasts
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			physiology
		                        			;
		                        		
		                        			Materia Medica
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Mice, Inbred BALB C
		                        			;
		                        		
		                        			Mouth Mucosa
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			Tissue Inhibitor of Metalloproteinase-1
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			metabolism
		                        			
		                        		
		                        	
10.CXCL12/SDF-1 alpha activates NF-kappaB and promotes oral cancer invasion through the Carma3/Bcl10/Malt1 complex.
International Journal of Oral Science 2009;1(3):105-118
AIMTo determine how SDF-1 alpha/CXCR4 activates nuclear factor-kappa B (NF-kappaB) and promotes oral squamous cell carcinoma (OSCC) invasion.
METHODOLOGYA lentivirus-based knockdown approach was utilized to deplete gene expression. NF-kappaB activation was evaluated by Western blot analysis and electrophoretic mobility shift (EMSA).
RESULTSWe show that the activation of NF-kappaB by CXCR4 occurs through the Carma3/Bcl10/Malt1 (CBM) complex in OSCC. We found that loss of components of the CBM complex in HNSCC can inhibit SDF-1 alpha induced phosphorylation and degradation of IkappaBalpha, while TNF alpha induced IKK activation remains unchanged. Further, we identified a role for novel and atypical, but not classical, PKCs in activating IKK through CXCR4. Importantly, inhibition of the CBM complex leads to a significant decrease in SDF-1 alpha mediated invasion of OSCC.
CONCLUSIONThe CBM complex plays a critical role in CXCR4-induced NF-kappaB activation in OSCC. Targeting molecular components of the NF-kappaB signaling pathway may provide an important therapeutic opportunity in controlling the progression and metastasis of OSCC mediated by SDF-1 alpha.
Adaptor Proteins, Signal Transducing ; antagonists & inhibitors ; physiology ; B-Cell CLL-Lymphoma 10 Protein ; CARD Signaling Adaptor Proteins ; antagonists & inhibitors ; physiology ; Carcinoma, Squamous Cell ; pathology ; Caspase Inhibitors ; Caspases ; physiology ; Cell Line, Tumor ; Chemokine CXCL12 ; antagonists & inhibitors ; physiology ; Enzyme Activation ; drug effects ; Gene Silencing ; Genetic Vectors ; genetics ; Humans ; I-kappa B Kinase ; drug effects ; I-kappa B Proteins ; metabolism ; Isoenzymes ; antagonists & inhibitors ; Lentivirus ; genetics ; Membrane Proteins ; antagonists & inhibitors ; physiology ; Mouth Neoplasms ; pathology ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein ; NF-KappaB Inhibitor alpha ; NF-kappa B ; antagonists & inhibitors ; physiology ; Neoplasm Invasiveness ; Neoplasm Proteins ; antagonists & inhibitors ; physiology ; Phosphorylation ; Plasmids ; genetics ; Protein Kinase C ; antagonists & inhibitors ; Receptors, CXCR4 ; physiology ; Tumor Necrosis Factor-alpha ; pharmacology
            
Result Analysis
Print
Save
E-mail