Ulcerative Colitis: Xu D

Chen Y, Gan H, Ouyang Q, Xu D, Pan Y, A Z. · Department of Life Sciences, Dali College, Dali 671000, China. · Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. · Pubmed #15553846 No free full text.

Abstract: The purpose of this study is to assess the effects of anti-inflammatory on activation of nuclear factor-kappaB and mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in intestinal mucosal biopsy specimens from patients with ulcerative colitis (UC). A total of 27 cases with UC were investigated. 15 cases received sulfasalazine (SASP) treatment or SASP and glucocorticoid treatment, 12 cases did not receive any medication related with UC. Normal mucosa from 9 colon cancer cases served as control. Ten pieces of intestinal mucosal biopsy specimens were obtained from each patient. The mRNA expression of ICAM-1 and VCAM-1 were determined by reversal transcription-polymerase chain reaction (RT-PCR). The protein levels of ICAM-1 and VCAM-1 were measured by enzyme linked immunosorbent assay (ELISA). NF-kappaB DNA binding activity was evaluated by electrophoretic mobility shift assay (EMSA). The results showed that NF-kappaB DNA binding activity, mRNA and protein expression of ICAM-1 and VCAM-1 were increased significantly in patients with UC, compared with normal control (P<0.05). Glucocorticoids and SASP markedly inhibited NF-kappaB activation and significantly decreased mRNA and protein expression of ICAM-1 and VCAM-1 (P<0.05). Adhesion molecules (ICAM-1 and VCAM-1) gene activation had significant positive correlation with the NF-kappaB DNA binding activity (r=0.8652 P<0.05, r=0.7902, P<0.05, respectively). We concluded that NF-kappaB is a major and essential factor in regulating the expression of adhesion molecules, it plays an important role in the pathogenesis of UC. SASP and glucocorticoids ameliorate UC via inhibition of NF-kappaB activation and reduction of adhesion molecules expression.

Eaton AD, Xu D, Garside P. · Division of Immunology, Infection & Inflammation, University of Glasgow, Western Infirmary, Glasgow, UK. · Immunology. · Pubmed #12562328 links to  free full text

Abstract: Interleukin-18 (IL-18), a pro-inflammatory member of the IL-1 family, has been associated with autoimmunity and allergic disease. This type of pathology is thought to be the result of a defect in immunological tolerance and is often observed in inflammatory disorders of the gut such as coeliac disease, Crohn's disease and ulcerative colitis. IL-18 has been implicated in a number of mucosal immune disorders, where it synergizes with IL-12 to induce the production of interferon-gamma (IFN-gamma). We have therefore investigated the effects of IL-18 and IL-12 administration on the induction of oral tolerance to ovalbumin. The suppression of specific Ig G2a production, delayed-type hypersensitivity responses and IFN-gamma production by antigen-specific T cells were all abrogated by the presence of exogenous IL-12 and IL-18, suggesting that oral tolerance was broken. The expression of the co-stimulatory molecule CD80 on dendritic cells was also shown to be increased by this combination of cytokines. As dendritic cells are thought to be of major importance in the induction of tolerance, this suggests a mechanism by which tolerance to mucosal antigens may be broken in vivo.