Increase in cyclooxygenase-2 and nitric oxide-synthase-2 mRNAs in pouchitis without modification of inducible isoenzyme heme-oxygenase-1.
OBJECTIVE
The pathophysiology of pouchitis occurring after ileal pouch-anal anastomosis remains controversial. Prostaglandins and nitric oxide synthesized in excess by cyclooxygenase-2 and nitric oxide synthase-2 are thought to be involved in the inflammatory process. Because heme oxygenase-1, by its antioxidant properties, could modulate inflammatory reaction, we analyzed mRNAs of the three enzymes (cyclooxygenase-2, nitric oxide synthase-2, and heme oxygenase-1) in patients with ileal pouch-anal anastomosis.


METHODS
Endoscopic biopsies were obtained in eight patients with normal ileal pouch-anal anastomosis, in eight patients with pouchitis, and in normal ileum of six healthy subjects. A relative quantitative RT-PCR was performed to determine the levels of cyclooxygenase-2, nitric oxide synthase-2, and heme oxygenase-1 mRNAs.


RESULTS
Cyclooxygenase-2 and nitric oxide synthase-2 mRNAs were increased both in normal ileal pouch-anal anastomosis and in pouchitis, compared with healthy subjects. Pouchitis disease activity index was correlated with mRNA levels of cyclooxygenase-2 (r = 0.71; p < 0.01) and nitric oxide synthase-2 (r = 0.51; p < 0.05). Heme oxygenase-1 mRNA levels were not significantly different in patients versus healthy subjects.


CONCLUSIONS
The increase in cyclooxygenase-2 and nitric oxide synthase-2 mRNA levels both in pouchitis and normal ileal pouch-anal anastomosis demonstrates that a latent inflammatory process occurs in the ileal pouch mucosa. This inflammatory process was not found to be associated with an induction of heme oxygenase mRNA, a possible regulator of the inflammatory response.
Leplingard
A
A
Appareil Digestif Environnement et Nutrition EA 1296, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, IFR No. 23, Rouen, France.
Brung-Lefebvre
M
M
Guédon
C
C
Savoye
G
G
Dechelotte
P
P
Lemoine
F
F
Lebreton
J P
JP
Lerebours
E
E
D000328:Adult; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D019449:Pouchitis / Q000201:enzymology* / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases