31 Mai A new therapeutic target to treat chronic inflammatory disease
Ulcerative Colitis is a chronic and relapsing inflammatory disease. Inflammation plays a major part in the symptoms of this disease that is characterized by pro-inflammatory cytokine production, leukocyte infiltration, and consequent structural and functional damage to the gut. There is still a lot that remains to be discovered about this condition and there is a great need for treatments.Controlled tissue cooling or hypothermia is widely used to suppress tissue damage. It can result in a reduction in inflammation. Recently, Transient Receptor Potential Melastatin–8 (TRPM8) was identified as a temperature-sensitive ion channel activated by mild cooling. As well as its thermos-sensation role, its acute activation or inhibition can have analgesic effects, suggesting that neuronal TRPM8 may also play a neurogenic anti-inflammatory role.
Researchers looked at the effect of TRPM8 activation, which very likely mediates some of the anti-inflammatory effects of mild cooling for peripheral inflammation, on tissue inflammation in the setting of experimental colitis. They worked on two mouse models of chemically induced colitis, 2,4,6-trinitrobenzenesulfonic acid (TNBS) and Dextran Sodium Sulfate (DSS). Among various chemically induced colitis models, the dextran sulfate sodium (DSS)-induced colitis model is widely used because of its simplicity and many similarities with human ulcerative colitis.
TRPM8 was found in the colon of the mice and was up-regulated in inflamed human and murine colon tissue. Its activation using the supercooling agent, icilin, had potent anti-inflammatory and disease-attenuating effects. Furthermore, icilin treatment reduced the 2,4,6-trinitrobenzenesulfonic acid–induced increase in levels of inflammatory cytokines and chemokines in the colon. In comparison with wild-type mice, Dextran Sodium Sulfate (DSS)-treated TRPM8 knockout mice showed elevated colonic levels of an inflammatory neuropeptide, although inflammatory indices were equivalent for both groups. The anti-inflammatory effect of TRPM8 is thus, in part, due to an inhibition of neuropeptide release.
The work helps define a new role for TRPM8. As well as its antinociception action, the molecule has anti-inflammatory properties which could be a new target for promising new therapies to treat inflammatory diseases such as colitis/IBD.
Syncrosome is an Efficacy Characterization preclinical CRO that offers relevant disease models, cutting-edge techniques and a comprehensive background of physiopathology to assist drug discovery companies. Syncrosome uses DSS-rodent for drug screening and efficacy testing for Inflammatory Bowel disease (including Crohn’s disease et Ulcerative colitis).
Key words: preclinical CRO, preclinical study, animal model, disease model, animal research, DSS model, DSS –mouse model, Inflammatory Bowel disease, Crohn’s disease, Ulcerative colitis, gastrointestinal tract, inflammation, cooling