OBJECTIVEThis study aimed to conduct a preliminary study on the possible role and significance of interleukin (IL)-12 and IL-27 in the pathogeneses of oral lichen planus (OLP).

METHODSThirty cases of patients with OLP (fifteen cases of reticular OLP and fifteen cases of erosive OLP) were enrolled in this study, and twenty cases of healthy people served as controls. Lymphocyte subsets CD3+, CD4+, CD8+, CD19+, and CD16+56 [natural killer cell (NK)] were tested using flow cytometry, and humoral immunity [immunoglobulin (Ig)G, IgA, IgM, C3, C4] were examined using nephelometry assays. IL-12 and IL-27 contents in serum of patients with OLP and normal controls were detected through enzyme linked immunosorbent assay. The correlations between the levels of IL-12, IL-27, immune status, and clinical characteristics of patients with OLP were analyzed, respectively.

RESULTSCD3+, CD4+, and CD8+in patients with OLP were markedly lower than the normal value, whereas CD 19+ of OLP in patients was significantly higher than the normal value (P<0.05). IgM inpatients with OLP was increased, whereas C4 was declined (P<0.05). IL-12 and IL-27 levels showed significant upregulation or ULF patients compared with control groups (P<0.05). Meanwhile, positive correlations existed between IL-12 andIL-27 levels in the serum of patients with OLP (r=0.912, P<0.01). No significant correlations of IL-12 and IL-27 epressions with clinical characteristics of OLP were found (P>0.05). Negative correlations of IL-12 and IL-27 levels with CD16+56(NK) cells were observed (r1 = -0.416, P1 = 0.022; r2 = -0.392, P2=0.032, respectively), whereas a positive correlation existed for IgG (r1=0.445, P1=0.014; n=0.549, P2=0.002, respectively).

CONCLUSIONA cellular immune dysfunction mainly dominate in patients with OLP, accompanied by some degree of humoral-immunity-function disorder. The abnormally high expressions of IL-12 and IL-27 are possibly synergized and promoted inflammation development in OLP. Its promotion takes place through the negatie feedback regulation of humoral immune responses, which are involved in the regulation of immune mechanisms of OLP.

Flow Cytometry ; Humans ; Immunoglobulins ; blood ; Interleukin-12 ; blood ; Interleukin-12 Subunit p35 ; metabolism ; Interleukin-27 ; blood ; Interleukins ; metabolism ; Killer Cells, Natural ; Lichen Planus, Oral ; blood ; immunology

OBJECTIVE: To assess the capability of phosphodiesterase type IV inhibitor (rolipram) to suppress IL-12 in human decidua and the subsequent changes of Th-2 cytokine (IL-10) and Th-1 cytokine (TNF-alpha). METHODS: Decidual tissues of 10 first-trimester pregnant women and 10 first-trimester pregnant women diagnosed as missed abortion were collected by dilatation and currettage. The decidual tissues were treated with rolipram for 6 hours. Protein and mRNA expression in the tissues were analysed by western blotting, immunohistochemistry and reverse transcription-polymerase chain reaction. RESULTS: Rolipram, in the concentration above 1 microgram/ml, could decrease the expression of IL-12p35 (control: 46.37+/-7.38, rolipram: 24.34+/-8.46) and IL-12p40 mRNA (control: 31.7+/-5.8, rolipram: 14.9+/-4.6) and protein (control: 52.4+/-8.9, rolipram: 40.9+/-12.1). However, the expression of IL-10 and TNF-alpha mRNA and protein did not changed by rolipram. There was no difference in the cytokine expression pattern between the decidual tissues of normal pregnancy and missed abortion. CONCLUSION: Rolipram, the phosphodiesterase type IV inhibitor, could induce the decrease of IL-12 in human decidua. In human decidual tissue, unlike other human tissues, the decrease of IL-12 by rolipram did not modulate other Th-1/Th-2 cytokines. Inability of IL-12 to modulate other Th-1/Th-2 cytokines might be related with unique cytokine network in human decidua rather than its small extent of decrease.
Abortion, Missed ; Blotting, Western ; Cyclic Nucleotide Phosphodiesterases, Type 4* ; Cytokines* ; Decidua ; Dilatation ; Female ; Humans* ; Immunohistochemistry ; Interleukin-10 ; Interleukin-12 Subunit p35 ; Interleukin-12 Subunit p40 ; Interleukin-12* ; Pregnancy ; Pregnant Women ; RNA, Messenger ; Rolipram ; Tumor Necrosis Factor-alpha

Cell Survival ; drug effects ; Cells, Cultured ; Dendritic Cells ; drug effects ; immunology ; physiology ; Humans ; Immunophenotyping ; Interleukin-10 ; pharmacology ; Interleukin-12 ; genetics ; secretion ; Interleukin-12 Subunit p35 ; Interleukin-12 Subunit p40 ; Protein Subunits ; genetics ; secretion ; RNA, Messenger ; analysis

IL-12 is a secretory heterodimeric cytokine composed of p35 and p40 subunits. IL-12 p35 and p40 subunits are sometimes produced as monomers or homodimers. IL-12 is also produced as a membrane-bound form in some cases. In this study, we hypothesized that the membrane-bound form of IL-12 subunits may function as a costimulatory signal for selective activation of TAA-specific CTL through direct priming without involving antigen presenting cells and helper T cells. MethA fibrosarcoma cells were transfected with expression vectors of membrane-bound form of IL-12p35 (mbIL-12p35) or IL-12p40 subunit (mbIL-12p40) and were selected under G418-containing medium. The tumor cell clones were analyzed for the expression of mbIL-12p35 or p40 subunit and for their stimulatory effects on macrophages. The responsible T-cell subpopulation for antitumor activity of mbIL-12p35 expressing tumor clone was also analyzed in T cell subset-depleted mice. Expression of transfected membrane-bound form of IL-12 subunits was stable during more than 3 months of in vitro culture, and the chimeric molecules were not released into culture supernatants. Neither the mbIL-12p35-expressing tumor clones nor mbIL-12p40-expressing tumor clones activated macrophages to secrete TNF-alpha. Growth of mbIL-12p35-expressing tumor clones was more accelerated in the CD8+ T cell-depleted mice than in CD4+ T cell-depleted or normal mice. These results suggest that CD8+ T cells could be responsible for the rejection of mbIL-12p35-expressing tumor clone, which may bypass activation of antigen presenting cells and CD4+ helper T cells.
Animals ; Antigen-Presenting Cells ; Clone Cells ; Corynebacterium ; Fibrosarcoma ; Interleukin-12 ; Interleukin-12 Subunit p35 ; Interleukin-12 Subunit p40 ; Macrophages ; Mice ; Rejection (Psychology) ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Tumor Necrosis Factor-alpha

OBJECTIVE: To investigate the mRNA level of IL-12, ICAM-1 and MCP-3 in human nasal epithelial cells. METHOD: Firstly, human primary nasal epithelial cells were cultured, and then 4 pairs of primers were designed for detecting mRNA level of IL-12, ICAM-1 and MCP-3. The 938 bp PCR products of GAPDH were used as internal standards. The mRNA expression levels of IL-12, ICAM-1 and MCP-3 in primary nasal epithelial cells was measured with semi-quantitative reverse transcription-polymerase chain reaction. RESULT: The round or irregular primary nasal epithelial cells were observed sticking to the bottom of cell culture plates under 400 times optical microscope. The expressions of IL-12 p35, ICAM-1 and MCP-3 mRNA were found in primary nasal epithelial cells while IL-12 p40 subunit was not detected. CONCLUSION IL-12 p35, ICAM-1 and MCP-3 mRNAs are expressed in primary nasal epithelial cells, whereas effective IL-12 with integrity is not present in nasal epithelial cells.
Cells, Cultured ; Chemokine CCL7 ; metabolism ; Epithelial Cells ; metabolism ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-12 Subunit p35 ; metabolism ; Nasal Mucosa ; cytology ; metabolism ; RNA, Messenger ; genetics

OBJECTIVE: To explore the expression of IL-35, Epstein-Barr virus-induced gene 3 (EBI3) mRNA and IL-12A mRNA in peripheral blood of patients with allergic rhinitis and its significance. METHOD: Peripheral blood were collected from patients with allergic rhinitis (46 cases) and healthy human controls(30 cases). The level of IL-35 in serum was measured by enzyme-linked immunosorbent assay. The subunit EB13 and IL-12A of IL-35 mRNA expressions in peripheral blood mononuclear cell(PBMC) were detected by SYBR Green real-time quantitative PCR. RESULT: IL-35 level in AR group (251.22 +/- 46.27) ng/L was significantly lower compared with that in the normal control group (382.17 +/- 25.41) ng/L, (P < 0.01). The mRNA expression level of EBI3 in the patients with allergic rhinitis was significantly lower than that in the normal control group (P < 0.01), AR group EB13 mRNA level was about half of that in the normal control group. But the mRNA expression level of IL-12A in the patients with allergic rhinitis has not significant difference with that in the normal control group (P > 0. 05). CONCLUSION The decrease of IL-35 and EBI3 mRNA in AR,indicated that IL-35 and EBl3 mRNA may play an important role in allergic rhinitis.
Adolescent ; Adult ; Case-Control Studies ; Child ; Female ; Humans ; Interleukin-12 Subunit p35 ; blood ; Interleukins ; blood ; Male ; Middle Aged ; Minor Histocompatibility Antigens ; Rhinitis, Allergic ; blood ; Young Adult

The aim of this study was to investigate the expression and immunologic regulation function of interleukin-23 and its related cytokines in chronic idiopathic thrombocytopenic purpura (ITP) patients. Levels of cytokines in peripheral blood mononuclear cells (PBMNC) were detected by reverse-transcription real-time polymerase chain reaction in 30 patients with chronic ITP and 15 healthy volunteers. The quantity of IL-23, IL-12, IL-17 in serum was detected by enzyme-linked immunosorbent assay (ELISA). The results showed that low detectable mRNA levels of IL-23p19, IL-12p35, IL-27 and IL-12p40 were found in all patients and healthy persons. Trace of IL-17 mRNA were expressed in PBMNC of part of patients and normal controls. Levels of IL-12p35, IL-27, IL-17 mRNA between healthy persons and chronic ITP patients were not statistically different. Compared with normal controls, patients showed the lower expression levels of IL-23p19 and IL-12p40 mRNA (p < 0.01). The IL-12 levels of chronic ITP patients were significantly higher than that of normal controls (p < 0.01). The IL-23 and IL-17 levels of chronic ITP patients were same to that of normal controls. It is concluded that the imbalance of T cell subsets in ITP patients mainly associated with IL-12, but not with IL-23 and IL-17.
Adolescent ; Adult ; Case-Control Studies ; Chronic Disease ; Female ; Humans ; Interleukin-12 ; metabolism ; Interleukin-12 Subunit p35 ; metabolism ; Interleukin-12 Subunit p40 ; metabolism ; Interleukin-17 ; metabolism ; Interleukin-23 ; metabolism ; Interleukin-23 Subunit p19 ; metabolism ; Male ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic ; metabolism ; Young Adult

BACKGROUND AND OBJECTIVES: The etiology and pathogenesis of nasal polyp are still ill-defined and have been debated for many years. Recently, the identification and localization of mRNA of cytokines, chemokines, and growth factors that may be involved in the formation of nasal polyp have been studied. But, transcription factors that control the expressions of cytokines have not been studied. The purpose of this study is to investigate IL-12 and IL-4 mRNA in the polyps of the patients with allergy-associated and nonallergy-associated chronic sinusitis and compared it with controls. IL-12 receptor and IRF-1, c-maf and GATA-3 which are transcription factors of IFN-gamma, IL-4 and IL-5, respectively were also studied. MATERIALS AND METHOD: Nasal polyp tissues were surgically obtained from two groups of patients with chronic sinusitis: those who had allergic rhinitis (n=) and those without allergy (n=3). The normal nasal mucosa from inferior turbinate were obtained from normal subjects. IL-12p35, IL-12p40, IL-12Rbeta2, IRF-1, IL-4, GATA-3 and c-maf mRNA expression were analysed by means of the reverse transcription and polymerase chain reaction and southern blot in three groups. RESULTS: The expression of IL-12p40, IL-12Rbeta2, IRF-1 mRNA were significantly higher in the nonallergic polyp group than in the control group (p<0.05). GATA-3 mRNA was significantly expressed in allergic polyp group than in the control group (p<0.05). CONCLUSION: These results suggest IL-12, IL-12Rbeta2 and IRF-1 may be involved in nonallergic polyp formation. GATA-3 may contribute to allergic polyp formation.
Blotting, Southern ; Chemokines ; Cytokines ; Gene Expression* ; Humans ; Hypersensitivity ; Intercellular Signaling Peptides and Proteins ; Interleukin-12 ; Interleukin-12 Subunit p35 ; Interleukin-12 Subunit p40 ; Interleukin-4 ; Interleukin-5 ; Nasal Mucosa ; Nasal Polyps* ; Polymerase Chain Reaction ; Polyps ; Receptors, Interleukin-12 ; Reverse Transcription ; Rhinitis ; RNA, Messenger ; Sinusitis ; Transcription Factors ; Turbinates

BACKGROUND/AIMS: Infection with hepatitis B virus (HBV) may result in various conditions. Natural course of HBV infection is influenced by various host immune factors and cytokines play a crucial role in host immune defense. This study was undertaken to investigate the association between HBV persistence and development of hepatocelluar carcinoma (HCC) and single nucleotide polymorphisms (SNPs) of interleukin (IL)-12A. METHODS: Between March 2002 and December 2004, seven hundred thirty Korean patients with HBV infection and 320 healthy individuals who recovered from HBV infection were enrolled. We assessed polymorphisms and haplotype in IL-12A, and the genotype distributions of the HBV clearance and persistence groups were compared in order to investigate the association between HBV persistence and SNPs of IL-12A. Moreover, the genotypic distributions between patients with HCC and without HCC were compared to investigate the association between the development of HCC and SNPs of IL-12A. RESULTS: We asssesed the SNPs of IL-12A at position +6400, +6624 and +7003. On the basis of logistic regression analysis, no statistically significant association with HBV persistence was observed with IL-12A exon 7 +6400, +6624, 3' UTR +7003 SNP and haplotype of IL-12A +6400/+6624/+7003. Furthermore, no statistically significant association of HCC development with IL-12A exon 7 +6400, +6624, 3' UTR +7003 SNP and haplotype of IL-12A +6400/+6624/+7003 was observed. CONCLUSIONS: These results suggest that SNPs and haplotype of IL-12A are not associated with HBV persistence and development of HCC. Further studies are needed to identify the host genetic factors in immune defense including cytokine gene polymorphisms of both IL-12A and IL-12B.
Adult ; Aged ; Carcinoma, Hepatocellular/etiology/*genetics/virology ; Female ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Hepatitis B/complications/*genetics ; Hepatitis B virus/isolation & purification ; Hepatitis B, Chronic/complications/*genetics ; Heterozygote ; Humans ; Interleukin-12 Subunit p35/*genetics ; Liver Neoplasms/etiology/*genetics/virology ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Retrospective Studies ; Risk Factors