title: The role of PPARgamma on restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction.
abstract: OBJECTIVE
  Psychological stress has been implicated in the clinical course of several gastrointestinal diseases, but the mechanisms implicated and the effects of stress on the normal colon are not yet fully understood.
  
  
  METHODS
  Male Wistar rats were exposed to various immobilization periods as a stress paradigm. Colon was processed to assess myeloperoxidase activity, nitric oxide synthase 2, cyclooxygenase 2, and peroxisome proliferator-activated receptor gamma (PPARgamma) expression and production of prostaglandins. Colonic permeability, bacterial translocation, tight junctions ultrastructure, and immunoglobulin (Ig) A levels were also evaluated.
  
  
  RESULTS
  Exposure to acute (6 hours) immobilization stress produced an increase in myeloperoxidase activity and nitric oxide synthase 2 and cyclooxygenase 2 expression. All these parameters remained increased after 5 days of repeated stress exposure, showing a trend to normalize after 10 days. Levels of the anti-inflammatory eicosanoid 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and expression of PPARgamma run parallel with these changes. Colonic epithelial barrier was altered after stress exposure, and a significant decrease in colonic IgA levels after acute stress exposure was observed. Pretreatment with PPARgamma agonists 15d-PGJ(2) and rosiglitazone prevented colonic inflammation and barrier dysfunction as well as the decrease of IgA production induced after acute stress; PPARgamma specific antagonist T0070907 reverted these effects.
  
  
  CONCLUSIONS
  Activation of PPARgamma in rat colon in vivo seems to counteract colonic inflammation and dysfunction induced by stress. On the other hand, PPARgamma ligands may be therapeutically useful in conditions in which inflammation and barrier dysfunction takes place in colon after exposure to stress.
authors.affiliation: Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid.
authors.forename: Angel
authors.initials: A
authors.lastname: Ponferrada
authors.forename: Javier R
authors.initials: JR
authors.lastname: Caso
authors.forename: Luis
authors.initials: L
authors.lastname: Alou
authors.forename: Arturo
authors.initials: A
authors.lastname: Colón
authors.forename: David
authors.initials: D
authors.lastname: Sevillano
authors.forename: María A
authors.initials: MA
authors.lastname: Moro
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lizasoain
authors.forename: Pedro
authors.initials: P
authors.lastname: Menchén
authors.forename: María L
authors.initials: ML
authors.lastname: Gómez-Lus
authors.forename: Pedro
authors.initials: P
authors.lastname: Lorenzo
authors.forename: Enrique
authors.initials: E
authors.lastname: Cos
authors.forename: Juan C
authors.initials: JC
authors.lastname: Leza
authors.forename: Luis
authors.initials: L
authors.lastname: Menchén
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology; D001549:Benzamides / Q000494:pharmacology; D003092:Colitis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000382:microbiology / Q000473:pathology / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology*; D007408:Intestinal Absorption / Q000502:physiology; D008024:Ligands; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000009:adverse effects; D000077154:Rosiglitazone; D013312:Stress, Physiological / Q000150:complications* / Q000503:physiopathology; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: C477819:15-deoxyprostaglandin J2; D001549:Benzamides; D008024:Ligands; D047495:PPAR gamma; D011725:Pyridines; C458508:T 0070907; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015230:Prostaglandin D2; D003345:Corticosterone