No evidence for an involvement of the p38 and JNK mitogen-activated protein in inflammatory bowel diseases

Georgia Malamut; Candice Cabane; Laurent Dubuquoy; Mathilde Malapel; Benoit Dérijard; Jérôme Gay; Cyrus Tamboli; Jean-Frédéric Colombel; Pierre Desreumaux

doi:10.1007/s10620-006-9116-2

No evidence for an involvement of the p38 and JNK mitogen-activated protein in inflammatory bowel diseases

Dig Dis Sci. 2006 Aug;51(8):1443-53. doi: 10.1007/s10620-006-9116-2. Epub 2006 Jul 13.

Authors

Georgia Malamut¹, Candice Cabane, Laurent Dubuquoy, Mathilde Malapel, Benoit Dérijard, Jérôme Gay, Cyrus Tamboli, Jean-Frédéric Colombel, Pierre Desreumaux

Affiliation

¹ INSERM 0114, Lille, F-59037, France.

PMID: 16838116
DOI: 10.1007/s10620-006-9116-2

Abstract

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. P38 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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Blotting, Western
Colitis, Ulcerative / chemically induced
Colitis, Ulcerative / drug therapy
Colitis, Ulcerative / metabolism*
Disease Models, Animal
Enzyme Inhibitors / therapeutic use
Female
Gene Expression
Humans
Imidazoles / therapeutic use
Inflammatory Bowel Diseases / genetics
Inflammatory Bowel Diseases / metabolism*
Interleukin-1 / genetics
Intestinal Mucosa / metabolism
JNK Mitogen-Activated Protein Kinases / metabolism*
Male
Mice
Mice, Inbred BALB C
Middle Aged
Polymerase Chain Reaction
Prognosis
Pyridines / therapeutic use
RNA, Messenger / genetics
Trinitrobenzenesulfonic Acid / toxicity
Tumor Necrosis Factor-alpha / genetics
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Enzyme Inhibitors
Imidazoles
Interleukin-1
Pyridines
RNA, Messenger
Tumor Necrosis Factor-alpha
Trinitrobenzenesulfonic Acid
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
SB 203580