RT Journal Article
T1 Ulcerative colitis impairs the acylethanolamide-based anti-inflammatory system reversal by 5-aminosalicylic acid and glucocorticoids
A1 Suárez, Juan
A1 Romero-Zerbo, Yanina
A1 Márquez, Lucia
A1 Rivera, Patricia
A1 Iglesias, Mar
A1 Bermúdez-Silva, Francisco J.
A1 Andreu, Montserrat
A1 Rodríguez de Fonseca, Fernando
K1 Amidohidrolasas
K1 Antiinflamatorios
K1 Colitis Ulcerosa
K1 Expresión Génica
K1 Glucocorticoides
K1 PPAR alfa
K1 PPAR gamma
AB 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.
PB Public Library of Science
YR 2012
FD 2012-05-25
LK http://hdl.handle.net/10668/842
UL http://hdl.handle.net/10668/842
LA en
NO Suárez J, Romero-Zerbo Y, Márquez L, Rivera P, Iglesias M, Bermúdez-Silva FJ, et al. Ulcerative colitis impairs the acylethanolamide-based anti-inflammatory system reversal by 5-aminosalicylic acid and glucocorticoids. PLoS ONE. 2012; 7(5):e37729
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 6, 2025