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oai:riuma.uma.es:10630/323072026-02-03T11:21:43Zcom_10630_2254col_10630_37953

Ulcerative colitis impairs the acylethanolamide-based anti-inflammatory system reversal by 5-aminosalicylic acid and glucocorticoids. Suárez-Pérez, Juan Romero-Zerbo, Silvana Yanina Márquez, Lucia Rivera-González, Patricia Iglesias, Mar Bermúdez Silva, Francisco Javier Andreu, Montserrat Rodriguez-de-Fonseca, Fernando Colitis ulcerosa - Investigación Enfermedad inflamatoria intestinal PPARa Ulcerative colitis Chronic inflamation Endocannabinoid system Glucocorticoids Studies in animal models and humans suggest anti-inflammatory roles on the N-acylethanolamide (NAE)-peroxisome proliferators activated receptor alpha (PPARα) system in inflammatory bowel diseases. However, the presence and function of NAE-PPARα signaling system in the ulcerative colitis (UC) of humans remain unknown as well as its response to active anti-inflammatory therapies such as 5-aminosalicylic acid (5-ASA) and glucocorticoids. Expression of PPARα receptor and PPARα ligands-biosynthetic (NAPE-PLD) and -degrading (FAAH and NAAA) enzymes were analyzed in untreated active and 5-ASA/glucocorticoids/immunomodulators-treated quiescent UC patients compared to healthy human colonic tissue by RT-PCR and immunohistochemical analyses. PPARα, NAAA, NAPE-PLD and FAAH showed differential distributions in the colonic epithelium, lamina propria, smooth muscle and enteric plexus. Gene expression analysis indicated a decrease of PPARα, PPARγ and NAAA, and an increase of FAAH and iNOS in the active colitis mucosa. Immunohistochemical expression in active colitis epithelium confirmed a PPARα decrease, but showed a sharp NAAA increase and a NAPE-PLD decrease, which were partially restored to control levels after treatment. We also characterized the immune cells of the UC mucosa infiltrate. We detected a decreased number of NAAA-positive and an increased number of FAAH-positive immune cells in active UC, which were partially restored to control levels after treatment. NAE-PPARα signaling system is impaired during active UC and 5-ASA/glucocorticoids treatment restored its normal expression. Since 5-ASA actions may work through PPARα and glucocorticoids through NAE-producing/degrading enzymes, the use of PPARα agonists or FAAH/NAAA blockers that increases endogenous PPARα ligands may yield similar therapeutics advantages. 2024-07-25T10:21:13Z 2024-07-25T10:21:13Z 2012 journal article VoR Suárez J, Romero-Zerbo Y, Márquez L, Rivera P, Iglesias M, Bermúdez-Silva FJ, et al. (2012) Ulcerative Colitis Impairs the Acylethanolamide-Based Anti-Inflammatory System Reversal by 5-Aminosalicylic Acid and Glucocorticoids. PLoS ONE 7(5): e37729. https://doi.org/10.1371/journal.pone.0037729 https://hdl.handle.net/10630/32307 10.1371/journal.pone.0037729 eng Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ open access application/pdf PLOS