title: Activation of protease-activated receptors (PARs)-1 and -2 promotes alpha-smooth muscle actin expression and release of cytokines from human lung fibroblasts.
abstract: Previous studies have shown that protease-activated receptors (PARs) play an important role in various physiological processes. In the present investigation, we determined the expression of PARs on human lung fibroblasts (HLF-1) and whether they were involved in cellular differentiation and pro-inflammatory cytokine and prostaglandin (PGE2) secretion. PAR-1, PAR-2, PAR-3, and PAR-4 were detected in fibroblasts using RT-PCR, immunocytochemistry, and flow cytometry. Increased expression of PAR-4, but not other PARs, was observed in fibroblasts stimulated with phorbol myristate acetate. The archetypical activators of PARs, namely, thrombin and trypsin, as well as PAR-1 and PAR-2 agonist peptides, stimulated transient increases in intracellular Ca(2+), and promoted increased α-smooth muscle actin expression. The proteolytic and peptidic PAR activators also stimulated the release of IL-6 and IL-8, as well as PGE2, with a rank order of potency of PAR-1 > PAR-2. The combined stimulation of PAR-1 and PAR-2 resulted in an additive release of both IL-6 and IL-8. In contrast, PAR-3 and PAR-4 agonist peptides, as well as all the PAR control peptides examined, were inactive. These results suggest an important role for PARs associated with fibroblasts in the modulation of inflammation and remodeling in the airway.
authors: School Pathology and Laboratory Medicine, University of Western Australia, 35 Stirling Highway, CrawleyPerth, WA, Australia School of Psychology and Clinical Sciences, Charles Darwin University, Ellengowan Drive, CasuarinaDarwin, NT, Australia.
authors: Nithiananthan
authors: N
authors: Asokananthan
authors: School Pathology and Laboratory Medicine, University of Western Australia, 35 Stirling Highway, CrawleyPerth, WA, Australia.
authors: Rommel S
authors: RS
authors: Lan
authors: School Pathology and Laboratory Medicine, University of Western Australia, 35 Stirling Highway, CrawleyPerth, WA, Australia.
authors: Peter T
authors: PT
authors: Graham
authors: School of Anatomy, Physiology and Human Biology, University of Western Australia, 35 Stirling Highway, CrawleyPerth, WA, Australia.
authors: Anthony J
authors: AJ
authors: Bakker
authors: School Pathology and Laboratory Medicine, University of Western Australia, 35 Stirling Highway, CrawleyPerth, WA, Australia.
authors: Ana
authors: A
authors: Tokanović
authors: School Pathology and Laboratory Medicine, University of Western Australia, 35 Stirling Highway, CrawleyPerth, WA, Australia.
authors: Geoffrey A
authors: GA
authors: Stewart
keywords: Cell differentiation; cytokines; inflammation; lung