Journal
INFLAMMATION RESEARCH
Volume 59, Issue 9, Pages 699-709Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00011-010-0181-9
Keywords
Bone marrow; Protease-activated receptor-2 (PAR(2)); Leukocytes; Inflammation; Colitis; Inflammatory bowel disease; Chimeric murine lines
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Funding
- Canadian Institute for Health Research
- Foundation Bettencourt Schueller
- Schlumberger Foundation
- Agence Nationale de la Recherche
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Our aim was to determine the contribution of proteinase-activated receptor-2 (PAR(2))-expressing bone marrow-derived cells on the development of colonic inflammation. Chimeric mice were generated by injecting bone marrow cells from wildtype (PAR (2) (+/+) ) or PAR(2) knockout mice (PAR (2) (-/-) ) into irradiated PAR (2) (+/+) or PAR (2) (-/-) mice. Treatments: Colitis was induced by giving 2.5% dextran sodium sulfate (DSS) solution for 7 days or by a single intracolonic administration of trinitrobenzene sulphonic acid (TNBS, 2 mg dissolved in 40% ethanol). Seven days after the induction of colitis, bowel thickness, inflammatory parameters [myeloperoxidase (MPO) activity, macroscopic/microscopic damage scores], and leukocyte trafficking (visualized via intravital microscopy) were assessed. Total deficiency of PAR(2) resulted in a marked reduction in severity of both TNBS and DSS induced colitis as assessed by MPO activity, macroscopic damage, bowel thickness, and leukocyte adherence. Colitis was attenuated in all chimeric lines in which there was loss of PAR(2) in the host, non-bone marrow-derived tissue, independent of the status of PAR expression by bone marrow-derived cells. Interestingly, TNBS colitis was attenuated in PAR (2) (+/+) chimeric mice with PAR (2) (-/-) derived bone marrow but these animals were not protected from DSS colitis. Expression of PAR(2) by host-derived tissues plays a dominant role in regulating colonic inflammation. PAR(2) expression by bone marrow-derived cells appears to play a role in TNBS colitis but not in DSS induced injury.
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