Changes Of Cytokines And Nuclear Factor κB In The Intestinal Muscosa Of Mice With Experimental Ulcerative Colitis

Recently,a large amount of studies have shown that T cell plays a key role in the pathogenesis of ulcerative colitis. T cell cytokines,especially Thl cytokines such as TFN-a and IL-1B were all proinflammatory cytokines. They were able to induce or aggregate intestinal inflammation.The expression of Thl cytokines was triggered by nuclear factor kappa B. This nuclear factor was normally located in the cytosol of the cell in the form of a complex. After activation,it would translocate into the nucleus and bind to its target sequence,that was usually a double strands DNA segment and trigger the expression of the downstream genes including TNF-a and IL-1B. The relationship between the expression of cytokines and the activation of NF-KB and the pathogenesis of UC had been investigeted. However,no conclusion had been drawn yet.In this study,we detected the expressions of cytokines and the activation of NF-xfi in mice with experimental UC and evaluated the relevance of them with the therapeutic effect of bifidobacterium.Methods:1 .Ulcerative colitis was induced in mice with the oral innoculation with DSS.2.The expressions of TNF-a,IL-1B in the intestinal mucosa of mice in acute or chronic stage of UC were detected by a semi-quantatitive assay,RT-PCR.3.The activation of NF-KB in the mucosa was evaluated by electrophoretic mobility shift assay (EMSA).4.The relevance of oral innuculation of Bf and the expression of cytokines and the activation of NF-KB were analyzied.Results:1.The establishment of the mouse model of UC:the typical symptoms ofcolitis including hematochezia diarrhea,loss of the body weight were observed in all mice after drinking DSS for about 3 to 5 days. Histological examination of intestinal mucosa under microscopy revealed mainly acute inflammatory changes including erosions and the infiltration of neutraphil and lymphocytes,etc. After 6 weeks of induction,the loss of integrity of intestinal epithelium and atrophy of the glands could be found associated with the infiltration of chronic inflammatory cells including lymphocytes and the formation of lympotic follicles. The histological changes of the animal model were similar to that of UC in humans.2.The expressions of cytokines and the activation of NF-icB:the expressions of TNF-a,IL-lp were increased in the intestinal mucosa in both acute and chronic stages of colitis. In addition,the nuclear binding activity of NF-xfl was also upregulated after the induction of colitis.3.The effect of bifidobacterium in the therapy of colitis:During the acute stage of colitis,both the symptoms and the lesions of the colonic mucosa were slighter in the animals orally innoculated with bifidobacterium during the induction of colitis than that of control. Furthermore,the expressions of TNF-a,IL-lp were decreased significantly compared with the control (p < 0.05). The activation of NF-icB was also suppressed. However,there was no difference discovered in the chronic stage of the diseases.Conclusion:l.Mice model induced by orally innoculation of DSS was a cheap,convenient,reproductable and reliable animal model of ulcerative colitis. The symptoms and histologcal changes were similar to that of UC in humans,thus it deserved the application widely in the study of ulcerative colitis.2.Proinflammatory cytokines play an important role in the pathogenesis of UC,potentially including the recruitment of infammtory celluas as well as the damage of intestinal mocosa. The expression of cytokines was modulated byNF-KB.3.Bf had both prophylactic and therapeutic effect on UC,especially in the acute stage of the disease. This was probably due to the suppression of the activity of NF-icB and the subsequent inhibition of the expression of proinfiammatory cytokines.