J Neurogastroenterol Motil.  2015 Jan;21(1):51-61. 10.5056/jnm14008.

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Affiliations
  • 1Department of Physiology, Keimyung University School of Medicine, Daegu, Korea.
  • 2Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea.
  • 3Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea. seenae99@dsmc.or.kr
  • 4Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.
  • 5Department of Microbiology, Kangwon National University School of Medicine, Chuncheon, Korea.
  • 6Department of Veterinary Physiology, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea. twkim@mail.knu.ac.kr
  • 7Department of Anatomy, Yeungnam University College of Medicine, Daegu, Korea.

Abstract

BACKGROUND/AIMS
Inflammatory bowel disease is commonly accompanied by colonic dysmotility and causes changes in intestinal smooth muscle contractility. In this study, colonic smooth muscle contractility in a chronic inflammatory condition was investigated using smooth muscle tissues prepared from interleukin-10 knockout (IL-10(-/-)) mice.
METHODS
Prepared smooth muscle sections were placed in an organ bath system. Cholinergic and nitrergic neuronal responses were observed using carbachol and electrical field stimulation with L-NG-nitroarginine methyl ester (L-NAME). The expression of interstitial cells of Cajal (ICC) networks, muscarinic receptors, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was observed via immunofluorescent staining.
RESULTS
The spontaneous contractility and expression of ICC networks in the proximal and distal colon was significantly decreased in IL-10(-/-) mice compared to IL-10(+/+) mice. The contractility in response to carbachol was significantly decreased in the proximal colon of IL-10(-/-) mice compared to IL-10(+/+) mice, but no significant difference was found in the distal colon. In addition, the expression of muscarinic receptor type 2 was reduced in the proximal colon of IL-10(-/-) mice. The nictric oxide-mediated relaxation after electrical field stimulation was significantly decreased in the proximal and distal colon of IL-10(-/-) mice. In inflamed colon, the expression of nNOS decreased, whereas the expression of iNOS increased.
CONCLUSIONS
These results suggest that damage to the ICC network and NOS system in the proximal and distal colon, as well as damage to the smooth muscle cholinergic receptor in the proximal colon may play an important role in the dysmotility of the inflamed colon.

Keyword

Colon; Contractility; Inflammatory bowel diseases; Interleukin-10

MeSH Terms

Animals
Baths
Carbachol
Colon*
Inflammatory Bowel Diseases*
Interleukin-10*
Interstitial Cells of Cajal
Mice
Mice, Knockout*
Muscle, Smooth
Nitrergic Neurons
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Receptors, Muscarinic
Relaxation
Carbachol
Interleukin-10
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Receptors, Muscarinic
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