The role of PPARgamma on restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction.
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.
Ponferrada
Angel
A
Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid.
Caso
Javier R
JR
Alou
Luis
L
Colón
Arturo
A
Sevillano
David
D
Moro
María A
MA
Lizasoain
Ignacio
I
Menchén
Pedro
P
Gómez-Lus
María L
ML
Lorenzo
Pedro
P
Cos
Enrique
E
Leza
Juan C
JC
Menchén
Luis
L
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
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