Article Text

other Versions

Download PDFPDF
Protease-Activated Receptor-2 activation: a major role in intestinal inflammation
  1. Eric Hyun
  1. University of Calgary, Canada
    1. Patricia Andrade-Gordon
    1. Johnson & Johnson Pharmaceutical Research Institute, United States
      1. Martin Steinhoff
      1. University of Munster, Germany
        1. Nathalie Vergnolle (nvergnol{at}
        1. University of Calgary, Canada


          Background & Aims: The role of PAR2 during intestinal inflammation is still unclear due to the fact that PAR2 activating peptide had both pro- and anti-inflammatory properties. The aim of this study was to investigate the effects of PAR2 deficiency (using PAR2-deficient mice: PAR2-/-) in models of colitis, in order to elucidate the role of endogenous PAR2 in the process of inflammation in the gut.

          Methods: Colonic inflammation in wildtype and PAR2-/- mice was induced by dextran sodium sulfate, trinitrobenzene sulphonic acid (a T-helper-1 predominant model) or oxazolone (a T-helper-2 predominant model). Leukocyte recruitment (assessed by intravital microscopy) and inflammatory parameters (myeloperoxydase, macro- and microscopic damage) were assessed during the development of colitis. Lastly, the protein levels of cyclooxygenases and adhesion molecules (ICAM-1, VCAM-1, Alpha-M, Alpha-4) were assessed via western blot analysis.

          Results: In all three models of colitis, MPO activity, macroscopic damage score and bowel thickness were significantly lower in PAR2-/- mice. Changes in vessel leukocyte recruitment parameters (rolling and adhesion) were also significantly reduced in PAR2-/- compared to wildtype mice after the induction of colitis. The protein expression of adhesion molecules (ICAM-1, VCAM-1 and alpha-4) was significantly attenuated, whereas the expression of COX-1 was significantly increased in PAR2-/- challenged with TNBS-induced colitis.

          Conclusions: The role of endogenous PAR2 in the gut is pro-inflammatory and independent of T-helper-1 or -2 cytokine profile. Endogenous PAR2 activation controls leukocyte recruitment in the colon and thus appears as a new potential therapeutic target for inflammatory bowel disease treatments.

          Statistics from

          Request Permissions

          If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

          Linked Articles

          • Digest
            Robin Spiller Magnus Simren