N-Acylethanolamine acid amidase (NAAA) inhibition rescues intestinal fibrosis through IL-23 pathway

Einleitung Intestinal fibrosis is a frequent complication in inflammatory bowel disease characterized by stricture formation and bowel obstruction. The pharmacological treatment is unsatisfactory, therefore, the elucidation of fibrosis mechanisms as well as the discovery of novel pharmacological treatments is a top priority [1] [2]. N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme responsible of the breakdown of N-acylethanolamides (NAEs) (i.e., palmitoylethanolamide PEA, anandamide AEA and oleoylethanolamide OEA). NAAA inhibition is reported to be effective in several inflammatory disorders including those affecting the intestine [3] and some NAEs counteract key mediators involved in organ fibrosis [4]. However, the role of NAAA and NAEs signalling in gut fibrosis is undiscovered to date.