Cyclooxygenase 2 mediates post-inflammatory colonic secretory and barrier dysfunction

Area of Science:

• Gastroenterology
• Inflammation research
• Epithelial biology

Background:

• Colitis impairs colonic epithelial barrier function, increasing bacterial translocation and inflammation.
• Persistent epithelial dysfunction after colitis resolution remains incompletely understood.
• Prostaglandin D2 (PGD2) is known to suppress colonic epithelial secretion.

Purpose of the Study:

• To investigate the role of PGD2 and cyclooxygenase-2 (COX-2) in post-colitis epithelial secretory and barrier dysfunction.
• To determine if COX-2 inhibition can ameliorate these persistent defects.

Main Methods:

• Induction of colitis in rats using trinitrobenzene sulphonic acid.
• Assessment of PGD2 synthesis and COX-2 expression post-colitis.
• In vitro measurement of colonic chloride secretion and bacterial translocation.
• Pharmacological inhibition of COX-2 (celecoxib, rofecoxib) and COX-1 (SC-560).

Main Results:

• Elevated PGD2 synthesis and COX-2 expression were observed 6 weeks post-colitis.
• Selective COX-2 inhibition reversed diminished colonic chloride secretion and reduced bacterial translocation.
• PGD2, but not its metabolite 15-deoxy-Delta(12-14)PGJ2, mimicked the secretory defect in normal tissue.

Conclusions:

• COX-2, likely through PGD2 generation, plays a critical role in sustained epithelial secretory and barrier dysfunction following colitis.
• Targeting COX-2 may offer a therapeutic strategy to restore colonic epithelial function after inflammatory insults.