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Activation of protease-activated receptors (PARs)-1 and -2 promotes alpha-smooth muscle actin expression and release of cytokines from human lung fibroblasts

Asokananthan, Nithiananthan, Lan, Rommel S., Graham, Peter T., Bakker, Anthony J., Tokanovié, Ana and Stewart, Geoffrey A. (2015). Activation of protease-activated receptors (PARs)-1 and -2 promotes alpha-smooth muscle actin expression and release of cytokines from human lung fibroblasts. Physiological Reports,3(Article No. e12295).

Document type: Journal Article
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IRMA ID 75039815xPUB990
Title Activation of protease-activated receptors (PARs)-1 and -2 promotes alpha-smooth muscle actin expression and release of cytokines from human lung fibroblasts
Author Asokananthan, Nithiananthan
Lan, Rommel S.
Graham, Peter T.
Bakker, Anthony J.
Tokanovié, Ana
Stewart, Geoffrey A.
Journal Name Physiological Reports
Publication Date 2015
Volume Number 3
Issue Number Article No. e12295
ISSN 2051-817X   (check CDU catalogue  open catalogue search in new window)
Total Pages 14
Place of Publication United Kingdom
Publisher John Wiley & Sons Ltd.
HERDC Category C1 - Journal Article (DIISR)
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 Ca2+, 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.
DOI http://dx.doi.org/10.14814/phy2.12295   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
 
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