Immunomodulatory role of proteinase-activated receptor-2.

Annals of the Rheumatic Diseases
Anne CrillyWilliam R Ferrell

Abstract

Proteinase-activated receptor-2 (PAR(2)) has been implicated in inflammatory articular pathology. Using the collagen-induced arthritis model (CIA) the authors have explored the capacity of PAR(2) to regulate adaptive immune pathways that could promote autoimmune mediated articular damage. Using PAR(2) gene deletion and other approaches to inhibit or prevent PAR(2) activation, the development and progression of CIA were assessed via clinical and histological scores together with ex vivo immune analyses. The progression of CIA, assessed by arthritic score and histological assessment of joint damage, was significantly (p<0.0001) abrogated in PAR(2) deficient mice or in wild-type mice administered either a PAR(2) antagonist (ENMD-1068) or a PAR(2) neutralising antibody (SAM11). Lymph node derived cell suspensions from PAR(2) deficient mice were found to produce significantly less interleukin (IL)-17 and IFNγ in ex vivo recall collagen stimulation assays compared with wild-type littermates. In addition, substantial inhibition of TNFα, IL-6, IL-1β and IL-12 along with GM-CSF and MIP-1α was observed. However, spleen and lymph node histology did not differ between groups nor was any difference detected in draining lymph node cell subse...Continue Reading

Citations

Jul 31, 2013·Journal of Medicinal Chemistry·Mei-Kwan YauDavid P Fairlie
Feb 6, 2014·American Journal of Obstetrics and Gynecology·Yifeng WangFenghua Liu
Nov 4, 2016·Cell Death & Disease·Ron PiranFred Levine
Feb 9, 2018·Nature Reviews. Rheumatology·Katerina OikonomopoulouVinod Chandran
Jun 8, 2018·Frontiers in Endocrinology·Kendal McCullochCarl S Goodyear
Nov 27, 2020·Biochemical Society Transactions·Kathryn A McIntoshRobin Plevin
Mar 26, 2021·Frontiers in Immunology·Fatima AbjiVinod Chandran

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