No Evidence for an Involvement of the P38 and JNK Mitogen-Activated Protein in Inflammatory Bowel Diseases

被引：0
作者：
Georgia Malamut
Candice Cabane
Laurent Dubuquoy
Mathilde Malapel
Benoit Dérijard
Jérôme Gay
Cyrus Tamboli
Jean-Frédéric Colombel
Pierre Desreumaux
机构：
[1] INSERM 0114,CHRU Lille
[2] Univ Lille 2,undefined
[3] Hôpital Huriez,undefined
[4] service des Maladies de I’Appareil Digestif et de la Nutrition,undefined
[5] UMR 6548-Centre National de la Recherche Scientifique,undefined
[6] Service de Gastroentérologie,undefined
来源：
Digestive Diseases and Sciences | 2006年 / 51卷
关键词：
Inflammatory bowel disease; Intestinal inflammation; P38 MAPK; JNK MAPK; TNBS; Colitis; SB203580;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Involvement of mitogen-activated protein (MAPK) in inflammatory bowel disease (IBD) remains enigmatic. We sought to evaluate the expression and activity of p38 and JNK MAPK in IBD and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and the effects of a p38 inhibitor, SB203580, in TNBS colitis. P 38 and JNK were quantified in colonic mucosa of 28 IBD patients and 19 controls and in 77 TNBS or control mice treated or not with SB203580. Colitis severity was assessed by survival, macroscopic and microscopic scoring, and molecular markers. Expression and activity of p38 and JNK were similar in IBD patients and controls and not modified by inflammation. In mice, p38 and JNK expression or activity did not increase following the induction of colitis. SB203580 decreased the p38 activity but displayed no clinical nor biological therapeutic effect. In conclusion, these results minimize the role of p38 and JNK in inflammatory colitis and the interest of p38 as a therapeutic target in IBD.
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页码：1443 / 1453
页数：10
相关论文
共 233 条
[1]  
Ghosh S(2002)Missing pieces in the NF-kappaB puzzle Cell 109 S81-S96
[2]  
Karin M(1997)Nuclear factor-kappa B: a pivotal transcription factor in chronic inflammatory diseases N Engl J Med 15 1066-1071
[3]  
Barnes PJ(2001)MAP kinases Chem Rev 101 2449-2476
[4]  
Karin M(2001)Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions Endocr Rev 22 153-183
[5]  
Chen Z(2003)p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases Nat Rev Drug Discov 2 717-726
[6]  
Gibson TB(1999)Differential expression and activation of p38 mitogen-activated protein kinase alpha, beta, gamma, and delta in inflammatory cell lineages J Immunol 162 4246-4252
[7]  
Robinson F(2001)Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation Physiol Rev 81 807-869
[8]  
Silvestro M(1998)Stabilization of interleukin-2 mRNA by the c-Jun NH2-terminal kinase pathway Science 280 1945-1949
[9]  
Pearson G(2002)P38 Mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease J Immunol 168 5342-5351
[10]  
Xu B(1996)Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function J Pharmacol Exp Ther 279 1453-1461
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