The anti-inflammatory pathway regulated via nicotinic acetylcholine receptors in rat intestinal mesothelial cells

Regulation of inflammation in intestinal mesothelial cells in the abdominal cavity is important for the pathogeny of clinical conditions, such as postoperative ileus, peritonitis and encapsulating peritoneal sclerosis. Here we have examined the inflammatory effect of lipopolysaccharide (LPS) and the anti-inflammatory effect of nicotinic acetylcholine receptor stimulation in rat intestinal mesothelial cells. LPS upregulated mRNA expression of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1) and inducible nitric oxide synthase (iNOS). The alpha 7, alpha 9 and alpha 10 subunits of nicotinic acetylcholine receptor were detected in intestinal mesothelial cells. Nicotine (10 nM) significantly inhibited LPS-induced mRNA expression of IL-1 beta and iNOS, but not TNF-a and MCP-1. In addition, the alpha 7 nicotinic acetylcholine receptor selective agonist, PNU-282987 (10 nM), significantly inhibited LPS-induced mRNA expression of IL-1 beta but not TNF-a, iNOS and MCP-1. Finally, we found that enteric nerves adhered to intestinal mesothelial cells located under the ileal serosa. In conclusion, intestinal mesothelial cells react to LPS to induce the production of nitric oxide from iNOS. The anti-inflammatory action of intestinal mesothelial cells expressing alpha 7nAChR may be mediated via their connectivity with enteric nerves.