The Plasma Kallikrein-Kininogen Pathway Is Critical in the Pathogenesis of Colitis in Mice

Frontiers in Immunology
Bo WangYi Wu

Abstract

The kallikrein-kinin system (KKS) consists of two serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-molecular-weight kininogen (HK). Upon activation of the KKS, HK is cleaved to release bradykinin. Although the KKS is activated in humans and animals with inflammatory bowel disease (IBD), its role in the pathogenesis of IBD has not been characterized. In the present study, we determined the role of the KKS in the pathogenesis of IBD using mice that lack proteins involved in the KKS. In two colitis models, induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS), mice deficient in HK, pKal, or bradykinin receptors displayed attenuated phenotypes, including body weight loss, disease activity index, colon length shortening, histological scoring, and colonic production of cytokines. Infiltration of neutrophils and inflammatory monocytes in the colonic lamina propria was reduced in HK-deficient mice. Reconstitution of HK-deficient mice through intravenous injection of HK recovered their susceptibility to DSS-induced colitis, increased IL-1β levels in the colon tissue and bradykinin concentrations in plasma. In contrast to the phenotypes of other mice lacking other proteins...Continue Reading

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Citations

Jul 22, 2018·Current Opinion in Hematology·Yi Wu
Oct 19, 2019·International Journal of Molecular Sciences·Hicham BenabdelkamelAssim A Alfadda
Oct 5, 2018·Frontiers in Endocrinology·Markku Lehto, Per-Henrik Groop
Jan 24, 2020·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Jeremy LagrangeVéronique Regnault
May 13, 2021·Research and Practice in Thrombosis and Haemostasis·Pradeep K SinghErin H Norris

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Methods Mentioned

BETA
transgenic
genotyping
PCR
Flow Cytometric
ELISA
Assay
enzyme-linked immunosorbent assay
flow cytometry

Software Mentioned

GraphPad
GraphPad Prism

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