Investigation Of Toll-like Receptor 4, CD14 And NF-κ B Expression In Ulcerative Colitis

Objectives: Toll-like receptors (TLRs) are transmembrance protein andreceptors of the innate immune system called pattern recognized receptors(PRRs).They recognize the microbial products refered as pathogen associated molecular patterns(PAMPs) ,mduce human innate immune system and control the adaptive immune system.TLR4 in association with MD-2 and CD14 is able to initiate introcelluar signals steps in response to LPS,which leads to NF- κ B activation ,cytokine expression and inflammation. Investigation the expression of Toll-like receptor 4 (TLR4),CD14 and NF- κ B on colonic mucosa of Ulcerative Colitis (UC) and the relationship between them were studied for illuminating the significance on the pathogenesis of the disease.Materials and Methods: Coionic biopsy specimens were collected fromactive UC and normal controls. The expression of TLR4,CD14 and NF- κ Bp65 were analyzed by immunohistochemistry(IHC). The results wereconfirmed by Western Blot. In UC, disease activity index (DAI) and pathological grade were classified according to Powell-Tuck grade system and Truelove-Richards system respectively.Results: Forty four UC cases and 12 normal controls entered the investigation. IHC and Western Blot revealed a significant increase of TLR4,CD14 and NF-k Bp65 antigen expression in colonic mucosa of UC compared with normal colonic mucosa (PO.001) . TLR4 and NF- k Bp65 were localized in epithelial cells and mononuclear cells in the lamina propria(LP).,and CD 14 was present in monocyte and neutrophil in LP. In UC TLR4,CD14 and NF- k Bp65 expression were positively related to DAI. (r=0.3&8,P=0.009; r=0.408,P=0.006; r=0.437,P=0.003 receptively). NF- k Bp65 significantly correlated with TLR4 and CD14 (r=0.839, PO.001; r=0.814, PO.001 receptively).TLR4 ,CD14 and NF- k Bp65 were positively related to pathological classification in UC. They were significantly higher in class II and class III than that in class I (P<0.001) as well as in class III than that in class II(P<0.001).Conclusions: The low or negative expression of TLR4 and CD14 in colonmay participate in the tolerance of colon mucosa to bacteria wall components .However in UC TLR4 CD 14 and NF- k B were upregulated significantly ,which to some extend reflect the degree of inflammation ,and thereby might contribute to occurrence and development of UC .