First published July 3, 2006 - More info
Proteinase-activated receptor–1 (PAR1), a G protein–coupled receptor activated by thrombin, is highly expressed in different cell types of the gastrointestinal tract. The activity of thrombin and of other proteinases is significantly increased in the colon of inflammatory bowel disease (IBD) patients. Since PAR1 activation in tissues other than the gut provoked inflammation, we hypothesized that PAR1 activation in the colon is involved in the pathogenesis of IBD. Here, we demonstrate that PAR1 is overexpressed in the colon of IBD patients. In mice, intracolonic administration of PAR1 agonists led to an inflammatory reaction characterized by edema and granulocyte infiltration. This PAR1 activation–induced inflammation was dependent on B and T lymphocytes. Moreover, PAR1 activation exacerbated and prolonged inflammation in a mouse model of IBD induced by the intracolonic administration of trinitrobenzene sulfonic acid (TNBS), while PAR1 antagonism significantly decreased the mortality and severity of colonic inflammation induced by TNBS and dextran sodium sulfate. In these 2 models, colitis development was strongly attenuated by PAR1 deficiency. Taken together, these results imply an important role for PAR1 in the pathogenesis of experimental colitis, supporting the notion that PAR1 inhibition may be beneficial in the context of IBD and possibly in other chronic intestinal inflammatory disorders.
Nathalie Vergnolle, Laurie Cellars, Andrea Mencarelli, Giovanni Rizzo, Sunita Swaminathan, Paul Beck, Martin Steinhoff, Patricia Andrade-Gordon, Nigel W. Bunnett, Morley D. Hollenberg, John L. Wallace, Giuseppe Cirino, Stefano Fiorucci
Original citation: J. Clin. Invest.114:1444 -1456 (2006). doi:10.1172/JCI21689
Citation for this retraction: J. Clin. Invest.116:2056 (2006). doi:10.1172/JCI21689R1
RT-PCR blots published in panel C of Figure 8 of this paper were mistakenly reproduced from a previous publication. The senior author sincerely regrets this error and would like to emphasize that this in no way diminishes the validity of the data contributed by the coauthors of the paper. However, the paper is being retracted in accordance with JCI policy.
The authors apologize for any inconvenience this error has caused.