IL-1beta inhibits intestinal smooth muscle proliferation in an organ culture system: involvement of COX-2 and iNOS induction in muscularis resident macrophages.

Abstract

Intestinal inflammation causes hyperplasia of smooth muscle that leads to thickening of the smooth muscle layer, resulting in dysmotility. IL-1beta is a proinflammatory cytokine that plays a central role in intestinal inflammation. In this study, to evaluate the effect of IL-1beta on proliferation of ileal smooth muscle cells in vivo, we utilized an organ culture system. When rat ileal smooth muscle tissue was cultured under serum-free conditions for 3 days, most smooth muscle cells maintained their arrangement and kept their contractile phenotype. When 10% FBS was added, an increased number of smooth muscle cells per unit area was observed. Moreover, immunohistochemical staining for PCNA demonstrated that FBS induced proliferation of smooth muscle cells. IL-1beta inhibited the proliferative effect of FBS. Furthermore, IL-1beta upregulated inducible nitric oxide (NO) synthase and cyclooxygenase-2 mRNA and protein and thus stimulated NO and PGE(2) productions. Moreover, exogenously applied NO and PGE(2) inhibited the increase of bromodeoxyuridine-positive cells stimulated with FBS. Immunostaining revealed that the majority of cyclooxygenase-2 and inducible NO synthase was located in the dense network of macrophages resident in the muscularis, which were immunoreactive to ED2. Based on these findings, IL-1beta acts as an anti-proliferative mediator, which acts indirectly through the production of PGE(2) and NO from resident macrophage within ileal smooth muscle tissue.

• Authors: Takashi Ohama, Masatoshi Hori, Eiichi Momotani, Margaret Elorza, William T Gerthoffer, Hiroshi Ozaki
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 292 Issue 5 Pg. G1315-22 (May 2007) ISSN: 0193-1857 [Print] United States
• PMID: 17234889 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Serum-Free
• Interleukin-1beta
• Proliferating Cell Nuclear Antigen
• RNA, Messenger
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Cyclooxygenase 2
• Ptgs2 protein, rat

Topics

• Animals
• Cell Proliferation (drug effects)
• Culture Media, Serum-Free
• Cyclooxygenase 2 (biosynthesis)
• Enzyme Induction
• Ileum (cytology, drug effects)
• Interleukin-1beta (pharmacology)
• Macrophages (physiology)
• Male
• Muscle, Smooth (cytology, drug effects)
• Nitric Oxide Synthase Type II (biosynthesis)
• Organ Culture Techniques
• Proliferating Cell Nuclear Antigen (biosynthesis)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar