INFLAMMATION AND INFLAMMATORY BOWEL DISEASE

Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E₁ and E₂ production by intestinal myofibroblasts

L E M Willemsen¹, M A Koetsier¹, S J H van Deventer², E A F van Tol¹

¹ Numico Research BV, Wageningen, the Netherlands
² Department of Experimental Internal Medicine, Academic Medical Centre, Amsterdam, the Netherlands

Correspondence to:
Correspondence to:
E A F van Tol, Department of Gastrointestinal Biology, Numico Research BV, PO Box 7005, 6700 CA Wageningen, the Netherlands;
ric.vantol{at}numico-research.nl

Background: The mucus layer protects the gastrointestinal mucosa from mechanical, chemical, and microbial challenge. Mucin 2 (MUC-2) is the most prominent mucin secreted by intestinal epithelial cells. There is accumulating evidence that subepithelial myofibroblasts regulate intestinal epithelial cell function and are an important source of prostaglandins (PG). PG enhance mucin secretion and are key players in mucoprotection. The role of bacterial fermentation products in these processes deserves further attention.

Aims: We therefore determined whether the effect of short chain fatty acids (SCFA) on MUC-2 expression involves intermediate PG production.

Methods: Both mono- and cocultures of epithelial cells and myofibroblasts were used to study the effects of SCFA on MUC-2 expression and PG synthesis. Cell culture supernatants were used to determine the role of myofibroblast derived prostaglandins in increasing MUC-2 expression in epithelial cells.

Results: Prostaglandin E₁ (PGE₁) was found to be far more potent than PGE₂ in stimulating MUC-2 expression. SCFA supported a mucoprotective PG profile, reflected by an increased PGE₁/PGE₂ ratio in myofibroblast supernatants and increased MUC-2 expression in mono- and cocultures. Incubation with indomethacin revealed the latter to be mediated by PG.

Conclusions: SCFA can differentially regulate PG production, thus stimulating MUC-2 expression in intestinal epithelial cells. This mechanism involving functional interaction between myofibroblasts and epithelial cells may play an important role in the mucoprotective effect of bacterial fermentation products.

Keywords: coculture; mucin; myofibroblast; prostaglandin; short chain fatty acid

Abbreviations: IBD, inflammatory bowel disease; COX, cyclo-oxygenase; NSAIDs, non-steroidal anti-inflammatory drugs; CC, coculture; MC, monoculture; PG, prostaglandins; SCFA, short chain fatty acids; MUC-2, mucin 2; BLU, light units

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