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Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice.
Dig Dis Sci. 2019 03; 64(3):729-739.DD

Abstract

BACKGROUND

The role of protease activated receptor-2 (PAR-2) in the pathogenesis of abdominal pain in irritable bowel syndrome (IBS) is not well defined.

AIMS

To investigate the role of PAR-2-mediated visceral hypersensitivity in a post-infectious IBS (PI-IBS) mouse model.

METHODS

T. spiralis-infected PI-IBS mouse model was used. Fecal serine protease activity and intestinal mast cells were evaluated. Intestinal permeability was assessed by urine lactulose/mannitol ratio, and colonic expressions of PAR-2 and tight junction (TJ) proteins were examined by Western blot. Intestinal immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was evaluated by abdominal withdrawal reflex in response to colorectal distention.

RESULTS

Colonic PAR-2 expression as well as fecal serine protease activity and intestinal mast cell counts were elevated in PI-IBS compared to the control mice. Decreased colonic TJ proteins expression, increased lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and visceral hypersensitivity were observed in PI-IBS compared to the control mice. Administration of PAR-2 agonist in control mice demonstrated similar changes observed in PI-IBS mice, while PAR-2 antagonist normalized the increased intestinal permeability and reduced visceral hypersensitivity observed in PI-IBS mice.

CONCLUSIONS

PAR-2 activation increases intestinal permeability leading to immune activation and visceral hypersensitivity in PI-IBS mouse model.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Du L
Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.
Long Y
Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China. longyanqin@zju.edu.cn.
Kim JJ
Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China. Division of Gastroenterology & Hepatology, Loma Linda University Health, Loma Linda, CA, 92354, USA.
Chen B
Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.
Zhu Y
Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.
Dai N
Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.

MeSH

Abdominal PainAnimalsColonFecesHyperalgesiaIrritable Bowel SyndromeMaleMast CellsMiceOligopeptidesPermeabilityReceptor, PAR-2Serine ProteasesSignal TransductionTh1 CellsTh1-Th2 BalanceTight JunctionsTrichinella spiralisTrichinellosis

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30446929

Citation

Du, Lijun, et al. "Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice." Digestive Diseases and Sciences, vol. 64, no. 3, 2019, pp. 729-739.
Du L, Long Y, Kim JJ, et al. Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice. Dig Dis Sci. 2019;64(3):729-739.
Du, L., Long, Y., Kim, J. J., Chen, B., Zhu, Y., & Dai, N. (2019). Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice. Digestive Diseases and Sciences, 64(3), 729-739. https://doi.org/10.1007/s10620-018-5367-y
Du L, et al. Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice. Dig Dis Sci. 2019;64(3):729-739. PubMed PMID: 30446929.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice. AU - Du,Lijun, AU - Long,Yanqin, AU - Kim,John J, AU - Chen,Binrui, AU - Zhu,Yubin, AU - Dai,Ning, Y1 - 2018/11/16/ PY - 2017/08/05/received PY - 2018/11/07/accepted PY - 2018/11/18/pubmed PY - 2019/8/6/medline PY - 2018/11/18/entrez KW - Intestinal permeability KW - Post-infectious irritable bowel syndrome KW - Protease activated receptor-2 KW - T helper KW - Tight junction SP - 729 EP - 739 JF - Digestive diseases and sciences JO - Dig Dis Sci VL - 64 IS - 3 N2 - BACKGROUND: The role of protease activated receptor-2 (PAR-2) in the pathogenesis of abdominal pain in irritable bowel syndrome (IBS) is not well defined. AIMS: To investigate the role of PAR-2-mediated visceral hypersensitivity in a post-infectious IBS (PI-IBS) mouse model. METHODS: T. spiralis-infected PI-IBS mouse model was used. Fecal serine protease activity and intestinal mast cells were evaluated. Intestinal permeability was assessed by urine lactulose/mannitol ratio, and colonic expressions of PAR-2 and tight junction (TJ) proteins were examined by Western blot. Intestinal immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was evaluated by abdominal withdrawal reflex in response to colorectal distention. RESULTS: Colonic PAR-2 expression as well as fecal serine protease activity and intestinal mast cell counts were elevated in PI-IBS compared to the control mice. Decreased colonic TJ proteins expression, increased lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and visceral hypersensitivity were observed in PI-IBS compared to the control mice. Administration of PAR-2 agonist in control mice demonstrated similar changes observed in PI-IBS mice, while PAR-2 antagonist normalized the increased intestinal permeability and reduced visceral hypersensitivity observed in PI-IBS mice. CONCLUSIONS: PAR-2 activation increases intestinal permeability leading to immune activation and visceral hypersensitivity in PI-IBS mouse model. SN - 1573-2568 UR - https://www.unboundmedicine.com/medline/citation/30446929/Protease_Activated_Receptor_2_Induces_Immune_Activation_and_Visceral_Hypersensitivity_in_Post_infectious_Irritable_Bowel_Syndrome_Mice_ DB - PRIME DP - Unbound Medicine ER -