P42 Intricate regulatory role of hydrogen sufide in dextran sulfate sodium-induced colitis

Abstract

Pathomechanism and treatment of inflammatory bowel disease still offer yet unresolved problems to science. Major involvement of transient receptor potential ankyrin 1 (TRPA1) receptors in animal models of Crohn’s disease and ulcerative colitis has been reported [1] . It has been shown recently that endogenous gaseous mediator hydrogen sulfide (H 2 S) activates TRPA1 receptors, releases neuropeptides and participates in cutaneous vasodilatation [2] . H 2 S is known to modulate inflammation, but precise mechanism of its action remains to be clarified. In the present study we investigated the role of exogenously applied and endogenous H 2 S as well as TRPA1 receptors in dextran sulfate sodium (DSS)-induced murine colonic inflammation. Preceding results of Engel and co-workers suggest a marked pro-inflammatory role of TRPA1 signalling in this model of ulcerative colitis. However, no data are available on the involvement of H 2 S-evoked TRPA1 receptor activation regarding colitis. Colitis was evoked by adding 2% DSS to the drinking water of TRPA1 WT and KO mice for 7 days. Some animal groups consumed water supplemented with H 2 S donor NaHS (100 mg/L). Other animal groups were injected with D,L-propargylglycine (PAG, 50 mg/kg, i.p. daily) to inhibit endogenous H 2 S synthesis. Clinical status of the animals was scored throughout the experiment. Myeloperoxidase (MPO) activity, interleukin-16 (IL-16) and soluble intercellular adhesion molecule 1 (sICAM-1) content of colon samples were determined. Histological evaluation of colon samples was performed. Our results conflict with those of Engel and colleagues indicating anti-inflammatory influence of TRPA1 receptors on the clinical condition in DSS-induced colitis. Our data regarding cellular inflammatory events reveal intricate regulation by endogenous and exogenous H 2 S. The gasotransmitter might exert both pro- and anti-inflammatory actions that might be mediated via TRPA1 receptor activation or different pathways. However, changes in neutrophil accumulation and cytokine secretion evoked by exogenous H 2 S or lack of endogenous H 2 S did not change clinical manifestation of colitis in TRPA1 WT mice.