2026-08-05T15:43:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/170402024-11-28T15:06:49Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
Suárez, Juan
author
Romero-Zerbo, Yanina
author
Márquez, Lucia
author
Rivera, Patricia
author
Iglesias, Mar
author
Bermúdez-Silva, Francisco J.
author
Andreu, Montserrat
author
Rodríguez de Fonseca, Fernando
authoraffiliation
[Suárez,J; Romero-Zerbo,Y; Rivera,P; Bermúdez-Silva,FJ; Rodríguez de Fonseca,F] Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Mediterranean Institute for the Advance of Biotechnology and Health Research Fundación, Málaga, Spain. [Márquez,L; Andreu,M] Department of Gastroenterology, Parc de Salut Mar, Universidad Autónoma, Barcelona, Spain. [Suárez,J; Bermúdez-Silva,FJ; Rodríguez de Fonseca,F] El Centro de Investigación Biomédica en Red de Fisiopatología de Obesidad y Nutrición, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain. [Iglesias,M] Department of Pathology, Parc de Salut Mar, Universidad Autónoma, Barcelona, Spain.
2024-01-15T18:16:50Z
2024-01-15T18:16:50Z
2012-05-25
10.1371/journal.pone.0037729
1932-6203
PloS One
http://hdl.handle.net/10668/842
22662201
http://hdl.handle.net/20.500.12105/17040
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.
eng
Amidohidrolasas
Antiinflamatorios
Colitis Ulcerosa
Expresión Génica
Glucocorticoides
PPAR alfa
PPAR gamma
Ulcerative colitis impairs the acylethanolamide-based anti-inflammatory system reversal by 5-aminosalicylic acid and glucocorticoids
research article