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- W4313368423 abstract "Abstract Thrombin can directly signal to innate immune cells via protease activating receptor-1 (PAR-1) but the functional consequence of receptor activation has yet to be fully defined. This study aims to assess the outcome of signalling through PAR-1 on monocytes in vivo. In a model of oxazolone-induced delayed type hypersensitivity (DTH)-contact dermatitis; inhibiting thrombin signalling via transgenic expression of hirudin on murine CD31 cells (Hir-Tg) significantly reduced ear swelling (ES) vs. wild type (WT) at 24 and 48 hours. The Hir-Tg mice had reduced CD68 cell recruitment and the recruited cells had a phenotype more polarised towards anti-inflammatory M2, with reduced iNOS, IFNγ & CCR2 expression, and increased expression of IL-10 and ABCA1. This phenotype was shown to be due to inhibition of thrombin signalling on the monocytes, as WT recipients of Hir-Tg bone marrow had a reduced ES, CD68 infiltration, granuloma and iNOS expression. Whereas Hir-Tg recipients (who would still express hirudin on the surface of endothelial cells) of WT bone marrow did not show a reduction in ES and behaved phenotypically akin to WT mice. Mice receiving IP-PAR1 antagonist prior to re-challenge had a similar reduction in ES and similar CD68 infiltration. This data shows that inhibiting thrombin signalling on the surface of innate immune cells both reduces recruitment in models of DTH and alters the behaviour of the cells to a more anti-inflammatory phenotype." @default.
- W4313368423 created "2023-01-06" @default.
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- W4313368423 date "2020-05-01" @default.
- W4313368423 modified "2023-09-25" @default.
- W4313368423 title "Inhibition of thrombin signalling on the surface of monocytes reduces inflammation in oxazolone-induced delayed type hypersensitivity" @default.
- W4313368423 doi "https://doi.org/10.4049/jimmunol.204.supp.144.4" @default.
- W4313368423 hasPublicationYear "2020" @default.
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