Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17040
Título
Ulcerative colitis impairs the acylethanolamide-based anti-inflammatory system reversal by 5-aminosalicylic acid and glucocorticoids
Autor(es)
Fecha de publicación
2012-05-25
Idioma
Inglés
Tipo de documento
research article
Resumen
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.
Palabras clave
Amidohidrolasas | Antiinflamatorios | Colitis Ulcerosa | Expresión Génica | Glucocorticoides | PPAR alfa | PPAR gamma
MESH
Adult | Aged | Amidohydrolases | Anti-Inflammatory Agents | Colitis, Ulcerative | Colon | Ethanolamines | Female | Gene Expression | Glucocorticoids | Humans | Intestinal Mucosa | Male | Mesalamine | Nitric Oxide Synthase Type II | PPAR alpha | PPAR gamma | Middle Aged | Young Adult | Adolescent | Phospholipase D
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