To investigate the expression of the subunit p65 of NF-kappaB and inhibitor kappa B alpha (IkappaBalpha) in mouse uterus during peri-implantation, thereby investigating whether transient activation of nuclear factor-kappaB (NF-kappaB) takes place during embryo implantation in mice. Immunohistochemical technique was used to examine the expression and localization of p65 in endometrium or deciduas, and Western blot analysis was employed to detect the levels of IkappaBalpha protein in mouse endometrium or deciduas. P65 protein was detected in stromal cells, epithelial cells of endometrium as well as in myometrium. Staining was predominately seen in the cytoplasm of the cells. Staining intensity for p65 was stronger in the epithelial compartment than the stromal compartment and myometrium. Staining intensity increased slightly during pregnancy, and it reached a high level on pregnancy day 5 and day 8. In contrast to p65, the level of IkappaBalpha protein was lowest on pregnancy day 5 in all groups. Our results suggested that NF-kappaB may regulate embryo implantation by its transient activation in mice.
Decidua/metabolism ; Embryo Implantation/*physiology ; Endometrium/metabolism ; I-kappa B Proteins/*biosynthesis ; NF-kappa B/*biosynthesis ; Time Factors ; Uterus/*metabolism ; Uterus/physiology

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint swelling and progressive destruction of cartilage and bone. Current RA treatments are largely empirical in origin and their precise mechanism of action is uncertain. Increasing evidence shows that chronic inflammatory diseases such as RA are caused by prolonged production of proinflammatory cytokines including tumor necrosis factor (TNF) and interleukin 1 (IL-1). The nuclear factor kappaB (NF-kappaB) plays an essential role in transcriptional activation of TNF and IL-1. NF-kappaB is induced by many stimuli including TNF and IL-1, forming a positive regulatory cycle that may amplify and maintain RA disease process. NF-kappaB and enzymes involved in its activation can be a target for anti-inflammatory treatment. Aspirin and sodium salicylate inhibit activation of NF-KB by blocking IkappaB kinase, a key enzyme in NF-kappaB activation. Glucocorticoids suppress expression of inflammatory genes by binding glucocorticoid receptor with NF-kappaB, and increasing expression of inhibitory protein of NF-kappaB, IkappaBalpha. Sulfasalazine and gold compounds also inhibit NF-kappaB activation. Continuing advances in our understanding of action mechanism of antirheumatic agents will benefit the future development of RA regimens with greater efficacy and less toxicity.
Animal ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/therapy* ; Arthritis, Rheumatoid/metabolism ; Arthritis, Rheumatoid/immunology ; Cytokines/immunology ; Cytokines/genetics ; Gene Expression Regulation ; Human ; Macrophages/immunology ; NF-kappa B/metabolism* ; NF-kappa B/immunology ; NF-kappa B/biosynthesis ; Tumor Necrosis Factor/genetics

T lymphocytes from patients with renal cell carcinoma (RCC) show reduced immune function and impaired activation of the transcription factor, NF-kappaB. We determined the mechanism of NF-kappaB suppression in T cells of RCC patient and determined whether supernatant fluid from RCC explants (RCC-S) induced the same phenotype of NF-kappaB suppression in normal T cells that is observed in patient T cells. The pattern of kappaB-binding activity in T cells of RCC patient was altered as compared to that seen in T cells obtained from normal volunteers. In some patients, no activation of RelA/NFkappaB1-binding activity was detectable, while in others kappaB-binding activity was modestly induced but the duration was reduced. IkappaBalpha was degraded normally following stimulation in both normal controls and T cells from RCC patients. RCC-S did not alter the cytoplasmic levels of RelA and NF-kappaB1 but did suppress their nuclear localization and inhibited the activation of RelA/NF-kappaB1 binding complexes. These results show that RCC-S can induce in normal T cells the same phenotype of impaired NF-kappaB activation that is detected in T cells of RCC patient. It also appears that NF-kappaB suppression by RCC-S may contribute to the immunosuppression of host immunity.
Carcinoma, Renal Cell/metabolism* ; Culture Media, Conditioned/metabolism ; DNA-Binding Proteins/biosynthesis ; Human ; Kidney Neoplasms/metabolism* ; NF-kappa B/metabolism* ; NF-kappa B/biosynthesis ; Proto-Oncogene Proteins/biosynthesis ; Proto-Oncogene Proteins c-rel ; T-Lymphocytes/metabolism* ; Tissue Culture

Animals ; Cyclooxygenase 2 ; biosynthesis ; genetics ; Female ; Liver Diseases, Alcoholic ; metabolism ; Male ; NF-kappa B ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cyclin D1 ; biosynthesis ; Hepatitis B virus ; Humans ; Liver ; pathology ; Liver Cirrhosis ; metabolism ; pathology ; NF-kappa B ; biosynthesis ; Trans-Activators ; biosynthesis

The role of nuclear factor kappaB in intestine injury induced by hepatic ischemia reperfusion was investigated. Eighteen male Wistar rats were divided into 3 groups randomly: sham operation group (group A), hepatic ischemia reperfusion group (group B) and hepatic ischemia reperfusion plus pyrrolidine dithiocarbamate (PDTC) group (group C). The rats in group A were only subjected to laparotomy, those in group B underwent partial hepatic ischemia reperfusion (ischemia for 1 h and reperfusion for 2 h) and those in group C underwent the same procedure as that of group B but received PDTC 200 mg/kg i.v. before and after ischemia. After reperfusion, tissues of jejunum and venous blood were obtained for measurement of TNF-alpha, MDA and MPO. The levels of TNF-alpha in jejunum and venous blood, the levels of MPO in jejunum in group B were significantly higher than those in group A and group C (P<0.05). There was no significant different in the levels of MDA between group B and group C. The severity of histological intestinal injury in group B and group C was similar. Hepatic ischemia reperfusion caused intestine injury, NF-kappaB may play an important role in this course and the targeting of upstream components of the inflammatory response, such as NF-kappaB, may have important therapeutic applications.
Animals ; Intestines ; pathology ; Liver ; blood supply ; metabolism ; Male ; NF-kappa B ; biosynthesis ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism

The role of nuclear factor kappaB in intestine injury induced by hepatic ischemia reperfusion was investigated. Eighteen male Wistar rats were divided into 3 groups randomly: sham operation group (group A), hepatic ischemia reperfusion group (group B) and hepatic ischemia reperfusion plus pyrrolidine dithiocarbamate (PDTC) group (group C). The rats in group A were only subjected to laparotomy, those in group B underwent partial hepatic ischemia reperfusion (ischemia for 1 h and reperfusion for 2 h) and those in group C underwent the same procedure as that of group B but received PDTC 200 mg/kg i.v. before and after ischemia. After reperfusion, tissues of jejunum and venous blood were obtained for measurement of TNF-alpha, MDA and MPO. The levels of TNF-alpha in jejunum and venous blood, the levels of MPO in jejunum in group B were significantly higher than those in group A and group C (P<0.05). There was no significant different in the levels of MDA between group B and group C. The severity of histological intestinal injury in group B and group C was similar. Hepatic ischemia reperfusion caused intestine injury, NF-kappaB may play an important role in this course and the targeting of upstream components of the inflammatory response, such as NF-kappaB, may have important therapeutic applications.
Intestines/*pathology ; Liver/*blood supply ; Liver/metabolism ; NF-kappa B/*biosynthesis ; Random Allocation ; Rats, Wistar ; Reperfusion Injury/*metabolism

To investigate the expression of the subunit p65 of NF-kappaB and inhibitor kappa B alpha (IkappaBalpha) in mouse uterus during peri-implantation, thereby investigating whether transient activation of nuclear factor-kappaB (NF-kappaB) takes place during embryo implantation in mice. Immunohistochemical technique was used to examine the expression and localization of p65 in endometrium or deciduas, and Western blot analysis was employed to detect the levels of IkappaBalpha protein in mouse endometrium or deciduas. P65 protein was detected in stromal cells, epithelial cells of endometrium as well as in myometrium. Staining was predominately seen in the cytoplasm of the cells. Staining intensity for p65 was stronger in the epithelial compartment than the stromal compartment and myometrium. Staining intensity increased slightly during pregnancy, and it reached a high level on pregnancy day 5 and day 8. In contrast to p65, the level of IkappaBalpha protein was lowest on pregnancy day 5 in all groups. Our results suggested that NF-kappaB may regulate embryo implantation by its transient activation in mice.
Animals ; Decidua ; metabolism ; Embryo Implantation ; physiology ; Endometrium ; metabolism ; Female ; I-kappa B Proteins ; biosynthesis ; Mice ; NF-KappaB Inhibitor alpha ; NF-kappa B ; biosynthesis ; Pregnancy ; Time Factors ; Uterus ; metabolism ; physiology

<b>OBJECTIVEb>To investigate the changes of NF-kappa B binding activity, the expression of PPARr and their correlation in the liver of rats with fatty liver disease (FLD) induced by different pathogenic factors and to investigate the molecular mechanism of the inflammation in FLD.

<b>METHODSb>40 Wistar rats were randomly divided into 4 groups of ten each: normal group, alcohol group, fat-rich diet group, alcohol adding fat-rich diet group. The rats were sacrificed at the end of the 16th week from the starting day of the experiment. Serum and liver specimens were collected. Histological specimens were stained with HE, SudanIV, and Masson and then studied microscopically. The ultrastructural changes were also checked under an electron microscope. NF-kappa B binding activity and the expression of PPARr mRNA were determined by electrophoretic mobility shift assay (EMSA) and RT-PCR respectively. The correlations between NF-kappa B binding activity and the expression of PPARr and the biochemical indexes were analyzed.

<b>RESULTSb>Steatosis, inflammation, necrosis and fibrosis were present in livers of the rats of all the experimental groups, and were most severe in the alcohol adding fat-rich diet group. NF-kappa B binding activity was markedly increased in the livers of the alcohol group (142+/-16.32) and of the alcohol adding fat-rich diet group (238+/-19.14) in comparison to the livers of the normal (73+/-9.24, F = 6.36, 17.93) and those of the fat-rich diet group (84+/-10.38, F = 5.96, 16.20). Binding activity was higher in the alcohol adding fat-rich diet group than that in the simple alcohol group, but there was no difference between those of the fat-rich diet and normal groups. The level of PPARr mRNA was lower in the livers of the alcohol, fat-rich diet, alcohol adding fat-rich diet groups (0.2530+/-0.069, 0.3647+/-0.082, 0.1226+/-0.054) than that of the controls (0.8097+/-0.094) (F = 15.43, 7.24, 21.45). NF-kappa B binding activity was correlated positively with the level of serum TNF alpha (r = 0.527, 0.639) and the content of MDA in the liver homogenates (r = 0.723, 0.537), but negatively with the expression of PPARr in the livers of the alcohol and the alcohol adding fat-rich diet groups (r = -0.568, -0.891).

<b>CONCLUSIONb>The enhanced nuclear factors NF-kappa B binding activity and decreased expression of PPARr play a pivotal role in the inflammatory response of FLD induced by alcohol and fat-rich diet. It may provide a new idea for treating FLD effectively.

Animals ; Fatty Liver ; metabolism ; Liver ; metabolism ; Male ; NF-kappa B ; metabolism ; PPAR gamma ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar

<b>OBJECTIVEb>To explore the expression of NF-kappaB and ICAM-1 in the gas explosion wounded lung of rats and the relationship.

<b>METHODSb>Digoxin labeled NF-kappaB was used as probe. In situ hybridization was performed to detect the NF-kappaB mRNA. Immunohistochemistry was used to detect the expression of NF-kappaB and ICAM-1.

<b>RESULTSb>The levels of NF-kappaB mRNA, the expression of NF-kappaB and ICAM-1 in the wounded rats were significantly increased and reached their peak two hours after injury. Pathology of lung tissue showed that some crachea epithelium mucosae were desquamated; congestion, edema of trachea wall and infiltration of neutrophilic granulocytes were found; hemorrhage, edema and infiltration of lots of inflammatory cells were present in alveolus cells. Electron microscope showed that type I, especially type II alveolus epithelia had degeneration and desquamation.

<b>CONCLUSIONb>The injury of gas explosion can activate NF-kappaB, which has close correlation with the acute injury to lung.

Animals ; Blast Injuries ; metabolism ; pathology ; Explosions ; Intercellular Adhesion Molecule-1 ; biosynthesis ; genetics ; Lung ; metabolism ; pathology ; NF-kappa B ; biosynthesis ; genetics ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley