Colonic mast cells trigger enteric neuronal death through the S100β/RAGE/NFκB pathway on inflammatory bowel diseases

Abstract

Ulcerative Rectocolitis (URC) and Crohn’s Disease (CD) are the main disorders belonging to the group of inflammatory bowel diseases (IBDs), whose etiologies are complex and involve environmental, microbiological, immunological and genetic factors. The lack of effective treatment makes the search for new targets for therapeutic approaches in the treatment of these diseases extremely important. One of the possible pathways may involve neuroimmune interaction, as several studies have demonstrated a close relationship between IBDs and the enteric nervous system (ENS). The neuroimmune interactions integrate the intestinal physiology and participate in the pathogenesis of inflammatory bowel diseases, with mast cells being one of the resident cells involved in the communication of the innate enteric immune system with the enteric nervous system. A study has shown that mast cell inactivation through its previous degranulation caused a reduction in the expression of the beta fraction of the calcium-binding protein S100 (S100β) during intestinal mucositis, suggesting a direct action of mast cell mediators in the ENS. S100β proteins are molecules whose expression in the intestine limits the enteric glial cells (EGCs) and that may be involved in the neuroinflammatory interference of these cells; also, their high concentration may be responsible for the death of neurons. Therefore, our hypothesis suggests that mast cells are involved in enteric neuronal death and in the worsening of the intestinal inflammatory process through increased expression of S100β protein and a consequent activation of the S100β/RAGE/NFκB pathway.