In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 288, No. 4 ( 2005-04), p. L734-L740
Abstract:
Pleural inflammation underlies many pleural diseases, but its pathogenesis remains unclear. Proteinase-activated receptor-2 (PAR 2 ) is a novel seven-transmembrane receptor with immunoregulatory roles. We hypothesized that PAR 2 is present on mesothelial cells and can induce pleural inflammation. PAR 2 was detected by immunohistochemistry in all (19 parietal and 11 visceral) human pleural biopsies examined. In cultured murine mesothelial cells, a specific PAR 2 -activating peptide (SLIGRL-NH 2 ) at 10, 100, and 1,000 μM stimulated a 3-, 42-, and 1,330-fold increase of macrophage inflammatory protein (MIP)-2 release relative to medium control, respectively ( P 〈 0.05 all) and a 2-, 32-, and 75-fold rise over the control peptide (LSIGRL-NH 2 , P 〈 0.05 all). A similar pattern was seen for TNF-α release. Known physiological activators of PAR 2 , tryptase, trypsin, and coagulation factor Xa, also stimulated dose-dependent MIP-2 release from mesothelial cells in vitro. Dexamethasone inhibited the PAR 2 -mediated MIP-2 release in a dose-dependent manner. In vivo, pleural fluid MIP-2 levels in C57BL/6 mice injected intrapleurally with SLIGRL-NH 2 (10 mg/kg) were significantly higher than in mice injected with LSIGRL-NH 2 or PBS (2,710 ± 165 vs. 880 ± 357 vs. 88 ± 46 pg/ml, respectively; P 〈 0.001). Pleural fluid neutrophil counts were higher in SLIGRL-NH 2 group than in the LSIGRL-NH 2 and PBS groups (by 40- and 26-fold, respectively; P 〈 0.05). This study establishes that activation of mesothelial cell PAR 2 potently induces the release of inflammatory cytokines in vitro and neutrophil recruitment into the pleural cavity in vivo.
Type of Medium:
Online Resource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.00173.2004
Language:
English
Publisher:
American Physiological Society
Publication Date:
2005
detail.hit.zdb_id:
1477300-4
SSG:
12
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