Colonic migrating motor complexes are inhibited in acute tri-nitro benzene sulphonic acid colitis

Inflammatory Bowel Disease (IBD) is characterized by overt inflammation of the intestine and is typically accompanied by symptoms of bloody diarrhea, abdominal pain and cramping. The Colonic Migrating Motor Complex (CMMC) directs the movement of colonic luminal contents over long distances. The tri-...

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Published in:	PloS one Vol. 13; no. 6; p. e0199394
Main Authors:	Hofma, Ben R, Wardill, Hannah R, Mavrangelos, Chris, Campaniello, Melissa A, Dimasi, David, Bowen, Joanne M, Smid, Scott D, Bonder, Claudine S, Beckett, Elizabeth A, Hughes, Patrick A
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 22-06-2018 Public Library of Science (PLoS)
Subjects:	Acids Activation Acute Disease Animals Benzene Benzenesulfonic acids Biology and Life Sciences Blood vessels Blood Vessels - pathology Body Weight Care and treatment CD11b antigen CD11b Antigen - metabolism Cell activation Cell migration Colitis Colitis - chemically induced Colitis - immunology Colitis - pathology Colitis - physiopathology Colon Colon - blood supply Colon - immunology Colon - pathology Colon - physiopathology Damage Development and progression Diarrhea Enteric nervous system Enzyme-linked immunosorbent assay Flow cytometry IL-1β Immune response Immunity, Innate Infiltration Inflammatory bowel disease Inflammatory bowel diseases Inhibition Interleukin-1beta - metabolism Intestinal Mucosa - pathology Intestine Male Medical research Medicine and Health Sciences Mice Mice, Inbred C57BL Microscopy Myoelectric Complex, Migrating Nerves Neurons - metabolism Nitrobenzene Pain Permeability Rodents Trinitrobenzenesulfonic Acid Australia Adelaide South Australia Australia
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Summary:	Inflammatory Bowel Disease (IBD) is characterized by overt inflammation of the intestine and is typically accompanied by symptoms of bloody diarrhea, abdominal pain and cramping. The Colonic Migrating Motor Complex (CMMC) directs the movement of colonic luminal contents over long distances. The tri-nitrobenzene sulphonic acid (TNBS) model of colitis causes inflammatory damage to enteric nerves, however it remains to be determined whether these changes translate to functional outcomes in CMMC activity. We aimed to visualize innate immune cell infiltration into the colon using two-photon laser scanning intra-vital microscopy, and to determine whether CMMC activity is altered in the tri-nitro benzene sulphonic (TNBS) model of colitis. Epithelial barrier permeability was compared between TNBS treated and healthy control mice in-vitro and in-vivo. Innate immune activation was determined by ELISA, flow cytometry and by 2-photon intravital microscopy. The effects of TNBS treatment and IL-1β on CMMC function were determined using a specialized organ bath. TNBS colitis increased epithelial barrier permeability in-vitro and in-vivo. Colonic IL-1β concentrations, colonic and systemic CD11b+ cell infiltration, and the number of migrating CD11b+ cells on colonic blood vessels were all increased in TNBS treated mice relative to controls. CMMC frequency and amplitude were inhibited in the distal and mid colon of TNBS treated mice. CMMC activity was not altered by superfusion with IL-1β. TNBS colitis damages the epithelial barrier and increases innate immune cell activation in the colon and systemically. Innate cell migration into the colon is readily identifiable by two-photon intra-vital microscopy. CMMC are inhibited by inflammation, but this is not due to direct effects of IL-1β.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0199394