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Objective To investigate the role of bacterial flagellin and CD98 in ulcerative colitis (UC).Methods A total of 60 first episode patients with active UC were recruited,including 30 mild and 30 moderate to severe UC cases.The serum of 30 healthy volunteers and normal intestinal tissues surgically removed from 15 colon cancer patients (more than 5 cm away from surgical margins) were collected as control.The content of bacterial flagellin antibodies in peripheral blood were measured with enzyme-linked immunosorbent assay (ELISA).The expression of CD98 in peripheral blood T lymphocyte was measured by flow cytometry (FACS).The expression of bacterial flagellin protein in intestinal mucosa and CD98 in intestinal epithelial basement membrane was tested by immunohistochemistry (IHC).The comparison between two groups was performed with the SNK-q method,the R×C table x2 test was used to analyze the counted data,and the Spearman correlation was used to analyze the rank materials.Results The peripheral blood concentration of bacteria flagella protein antibody of control group,mild UC group and moderate to severe group showed an upward trend,which was (7.603±2.118) pg/ml,(13.702±3.131) pg/ml and (20.813±3.004) pg/ml respectively,and the differences among groups were statistically significant (F=13.57,P＜0.01).The expression percentage of bacteria flagella protein in intestinal mucosa of the three groups also showed an upward trend,which was 3/15,56.67％ and 73.33％ respectively,and the differences among groups were statistically significant (x2 =11.553,P=0.003).The positive rate of CD98 expression in peripheral blood T lymphocytes of the three groups showed an upward trend,which was (28.42±4.31)％,(32.45±6.71)％ and (43.40±5.09) ％ respectively,and the differences among groups were statistically significant (x2 =10.110,P=0.007).The positive rate of CD98 expression in intestinal epithelial cells of the three groups also showed an upward trend,which was 1/15,36.67 ％ and 66.67％ respectively,and the differences among groups were statistically significant (x2 =5.400,P＜0.05).There was positive correlation between the peripheral blood concentration of bacteria flagella protein antibody and the expression of CD98 in peripheral blood T lymphocytes (r=0.548,P＜0.05).Conclusion Bacterial flagellin and CD98 may be important factors causing inflammatory reaction activity in UC.
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CD98 is a transmembrane heterodimer of cell surface.It regulates cell signaling pathway by activating some correlated proteins,and controls cell polarization,proliferation,adhesion and migration.CD98 plays an important role in the development of cancer and may be a novel tumor marker for diagnosis and prognosis in lung cancer.
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CD98, a disulfide-linked 125-kDa heterodimeric type II transmembrane glycoprotein, regulates beta 1 integrin- mediated cell adhesion. However, the molecular mechanisms underlying CD98-mediated activation of beta 1 integrin are presently unclear. In this study, the effects of CD98 signaling on the expression and clustering of beta 1 integrin were investigated. Activation of CD98 augmented surface expression of beta 1 integrin on MCF-7 cells. Cross-linking CD98 induced clustering of beta 1 integrins. Inhibition of phosphorylation of focal adhesion kimase (FAK) by PP2, an inhibitor of Src family kinase, reduced cell-extracellular matrix adhesion, but not surface expression and clustering of beta1 integrin on MCF-7 cells. This result was confirmed by over-expression of dominant negative forms of FAK. In addition, phalloidin or cytochalasin D inhibited CD98-mediated induction of cell-ECM adhesion, but not surface expression and clustering of b1 integrins. The inhibitory effects of PP2, cytochalasin D or phalloidin on CD98-stimulated cell adhesion were diminished by pretreatment of cells with Mn2+, which is shown to induce conformational change of integrins. These results provide the first evidence that CD98 activation increases not only beta1 integrin affinity but also its surface expression and clustering and the latter is independent of FAK/Src and cytoskeleton.