BACKGROUND: Crohn's disease is characterised by a chronic relapsing inflammation of the bowel in which proinflammatory cytokines play an important perpetuating role. Mitogen activated protein kinase p38 (p38 MAPK) has been established as a major regulator of the inflammatory response, especially with regard to production of proinflammatory cytokines, but its role in inflammatory bowel disease is unexplored. In this paper we describe the effects of a specific p38 MAPK inhibitor, SB 203580, in trinitrobenzene sulphonic acid (TNBS) induced colitis in mice. RESULTS: SB 203580 had a dichotomal effect in TNBS mice. Weight loss of TNBS mice treated with SB 203580 was significantly worse and colon weight on sacrifice was significantly increased in MAPK inhibitor treated TNBS mice (229.2 mg and 289.1 mg, respectively). However, the total number of cells in the caudal lymph node decreased to 188.8 x 10(4) cells in SB 203580 treated TNBS mice compared with 334 x 10(4) cells in vehicle treated mice. CD3/CD28 double stimulated caudal lymph node cells of SB 203580 treated mice showed decreased interferon gamma production but increased tumour necrosis factor alpha production. The concentration of interleukin 12p70 in colon homogenates was significantly decreased in SB 203580 treated mice whereas concentrations of interleukin 12p40, tumour necrosis factor alpha, and interleukin 10 were similar in vehicle and SB 203580 treated TNBS mice. CONCLUSION: Our results reveal a dichotomy in p38 MAPK action during experimental colitis.
BACKGROUND:Crohn's disease is characterised by a chronic relapsing inflammation of the bowel in which proinflammatory cytokines play an important perpetuating role. Mitogen activated protein kinase p38 (p38 MAPK) has been established as a major regulator of the inflammatory response, especially with regard to production of proinflammatory cytokines, but its role in inflammatory bowel disease is unexplored. In this paper we describe the effects of a specific p38 MAPK inhibitor, SB 203580, in trinitrobenzene sulphonic acid (TNBS) induced colitis in mice. RESULTS:SB 203580 had a dichotomal effect in TNBSmice. Weight loss of TNBSmice treated with SB 203580 was significantly worse and colon weight on sacrifice was significantly increased in MAPK inhibitor treated TNBSmice (229.2 mg and 289.1 mg, respectively). However, the total number of cells in the caudal lymph node decreased to 188.8 x 10(4) cells in SB 203580 treated TNBSmice compared with 334 x 10(4) cells in vehicle treated mice. CD3/CD28 double stimulated caudal lymph node cells of SB 203580 treated mice showed decreased interferon gamma production but increased tumour necrosis factor alpha production. The concentration of interleukin 12p70 in colon homogenates was significantly decreased in SB 203580 treated mice whereas concentrations of interleukin 12p40, tumour necrosis factor alpha, and interleukin 10 were similar in vehicle and SB 203580 treated TNBSmice. CONCLUSION: Our results reveal a dichotomy in p38 MAPK action during experimental colitis.
Authors: P R Young; M M McLaughlin; S Kumar; S Kassis; M L Doyle; D McNulty; T F Gallagher; S Fisher; P C McDonnell; S A Carr; M J Huddleston; G Seibel; T G Porter; G P Livi; J L Adams; J C Lee Journal: J Biol Chem Date: 1997-05-02 Impact factor: 5.157
Authors: R Beyaert; A Cuenda; W Vanden Berghe; S Plaisance; J C Lee; G Haegeman; P Cohen; W Fiers Journal: EMBO J Date: 1996-04-15 Impact factor: 11.598
Authors: Xue Hua Pang; Tian Ke Li; Qin Xie; Fu Qian He; De Jun Cui; You Qin Chen; Xiao Li Huang; Hua Tian Gan Journal: Int J Colorectal Dis Date: 2010-06-05 Impact factor: 2.571
Authors: G Docena; L Rovedatti; L Kruidenier; A Fanning; N A B Leakey; C H Knowles; K Lee; F Shanahan; K Nally; P G McLean; A Di Sabatino; T T MacDonald Journal: Clin Exp Immunol Date: 2010-08-20 Impact factor: 4.330