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

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.

Comparison of Changes in the Interstitial Cells of Cajal and Neuronal Nitric Oxide Synthase-positive Neuronal Cells With Aging Between the Ascending and Descending Colon of F344 Rats

“…After discarding 1 cm from the cecum and anus, 5 cm of the proximal and distal parts of the colon were collected from each. 33,39 A part of each sample 1 cm in length was prepared for histological analysis by fixation in 10% buffered formalin. The tissue specimens embedded in paraffin blocks were cut perpendicularly to the lumen into 4 μm thick sections and then stained with hematoxylin and eosin.…”

Hibiscus Sabdariffa L. Flowers and Olea Europea L. Leaves Extract-Based Formulation for Hypertension Care: In Vitro Efficacy and Toxicological Profile

“…In fact, in pathological conditions characterized by inflammation, gut segment spontaneous contractility is altered. 35 Pres Phytum affects spontaneous contractility of stomach, but no effect is obtained at the concentration effective on the cardiovascular system. This effect may result in a slight decrease of gastric emptying frequency.…”

Does Decreased c-KIT Expression in Myenteric Interstitial Cells of Cajal Cause Decreased Spontaneous Contraction in Murine Proximal Colon?

“…The findings from this paper suggest that IL-10 immunodeficient mice might be an attractive model for researching IBD including Crohn's disease. 1,5 In addition, this study's investigation of the function and expression level of muscarinic type 2 (M 2 ) receptors is worthwhile in that the M 2 receptors may play a greater role in the inflamed colon. 6,7 These considerations make the article a strong one, and its conclusions can serve as a stepping stone to investigate several unanswered problems in gastrointestinal (GI) smooth muscle biology as follows.…”

“…4 The animal model used in this study, however, showed inflammatory cell infiltration in all colonic layers (including the muscular layer) and exhibited lesions similar to those found in Crohn's disease. 1 This paper does take a novel approach by studying changes in smooth muscle and motility in an immunodeficiency model. The findings from this paper suggest that IL-10 immunodeficient mice might be an attractive model for researching IBD including Crohn's disease.…”

“…It also exhibited a decreased cholinergic response, caused by lowered expression of muscarinic receptors in the proximal colon and decreased neuronal nitric oxide synthase expression in both proximal and distal colon. 1 For the past decades, more than 60 different animal models have been applied to study inflammatory bowel disease (IBD), which can be divided into chemically induced, cell-transfer, congenital mutant and genetically engineered models.…”