The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases.

Mathilde Body-Malapel 1 Madjid Djouina 1 Christophe Waxin 1 Audrey Langlois 1 Corinne Gower 1 Philippe Zerbib 1 A-M Schmidt Pierre Desreumaux 1 Eric Boulanger 1 Cécile Vignal 1
1 LIRIC - Lille Inflammation Research International Center
Abstract : Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions of the intestinal tract. IBD are believed to result from an inappropriate immune response against the intestinal flora in genetically predisposed patients. The precise etiology of these diseases is not fully understood, therefore treatments rely on the dampening of symptoms, essentially inflammation, rather than on the cure of the disease. Despite the availability of biologics, such as anti-TNF antibodies, some patients remain in therapeutic failure and new treatments are thus needed. The multiligand receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in inflammatory reactions and immune system activation. Here, we investigated the role of RAGE in intestinal inflammation and its potential as a therapeutic target in IBD. We showed that RAGE was upregulated in inflamed tissues from IBD patients compared to controls. Rage(-/-) mice were less susceptible to intestinal and colonic inflammation development than WT mice. WT mice treated with the RAGE-specific inhibitor FPS-ZM1 experienced less severe enteritis and colitis. We demonstrated that RAGE could induce intestinal inflammation by promoting oxidative stress and endothelial activation which were diminished by FPS-ZM1 treatment. Our results revealed the RAGE signaling pathway as a promising therapeutic target for IBD patients.
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Mathilde Body-Malapel, Madjid Djouina, Christophe Waxin, Audrey Langlois, Corinne Gower, et al.. The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases.. Mucosal Immunology, Nature Pub. Group, 2018, 12, pp.468-478. ⟨10.1038/s41385-018-0119-z⟩. ⟨hal-02149337⟩

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