Toll-like Receptors2and4and Nuclear Factor-KB In Colonic Mucosa Of Ulcerative Colitis:Expression And Clinical Significance

Objective:To investigate expression of Toll-like receptors2and4(TLR2、TLR4) and nuclear factor-K B(NF-κB) in colonic mucosa of ulcerative colitis.Methods:Collect70patients diagnosed by Qi-Lu hospital of Shandong University and44patients in the control group. Immunohistochemistry was performed to examine the expression of TLR2、TLR4and NF-κB in colonic mucosa of UC (n=70). Normal mucosa of colon polyps was included as a control (n=44). x2test was performed to analyze the difference of TLR2, TLR4and NF-κB expression between UC group and normal control group, and to analyze the difference of TLR2, TLR4and NF-κB expression in different pathological damage of UC group. Pearson rank correlation was performed to analyze the correlation between TLR4and NF-κB,and correlation between TLR2and NF-κB.Result:TLR2, TLR4and NF-κB protein in UC group and in control group are present in the cytoplasm and cell nucleus, positive dyeing as yellow particles. The three proteins in UC group significantly express surface epithelial cells in the colonic mucosa, fossae epithelium, and single nuclear cells in inherent layer. The three proteins in control group express weekly or don’t express surface epithelial cells in the colonic mucosa, scattered inflammatory cells in inherent layer. The difference between expression of the three proteins in UC group and in control group has statistical significance (P<0.01). TLR2, TLR4and NF-κB protein in active period of UC mucous membrane tissues positive expression rate respectively100%,92.9%and100%. TLR2, TLR4and NF-κB protein in non-active period of UC mucous membrane tissues positive expression rate respectively28.6%,38.1%and38.1%. The difference between expression of the three proteins in active period and in non-active period has statistical significance (P<0.01). TLR2, TLR4and NF-κB expression of the number of positive cells are tending to increase gradually with increased endoscopic classification. Ⅲ level, II level are higher than I level (P<0.05, P<0.05), and III level is higher than II level (P<0.05).In UC group TLR2, TLR4and NF-kB protein all positive expression are34cases, and all negative expression are22cases. Pearson correlation analysis shows that NF-κB protein expression positively correlate with TLR2protein expression and TLR4protein expression in UC tissue (r=0.823, P<0.01; r=0.752, P<0.01)Conelusion:UC is a kind of inflammatory disease involving the rectum and colonic mucosa. Currently most scholars believe that abnormal immune response of the immune system to normal intestinal flora is the major factor in its pathogenesis. TLRs are the key factor to start the reaction of the innate immune defense through the recognition of PAMPs and their corresponding ligands to activate the innate immune response. TLRs selective combine with ligand, through the signal transduction intestinal mucosa mediated the immune response. Specific process consists of multiple interrelated signal transduction pathways, of which more in-depth study of TLRs-MyD88-IRAK-NF-KB transduction pathway. TLRs combine with corresponding ligands, and then through this way to activate various proinflammtory cytokines (eg TNF-a and IL-12) transcription and to mediate the natural immune response of intestinal mucosa. In control group intestinal mucosa epithelial cells trace express or don’t express TLR2, TLR4and NF-KB, and in UC group intestinal mucosa epithelial cells significantly express three proteins, so the difference between two groups is statistically significant. In UC group TLR2and TLR4and NF-KB expression in endoscopic grading there is significant difference between Ⅰ,Ⅱ,Ⅲ level, and its expression level with UC endoscopic classification and disease activity is closely related to. TLR2and TLR4positively correlate to NF-KB, which suggests that TLR2and TLR4through a series of signal transduction to activate NF-KB and to mediate intestinal mucosal immune response.