The Coagulant Factor Xa Induces Protease-Activated Receptor-1 and Annexin A2-Dependent Airway Smooth Muscle Cytokine Production and Cell Proliferation

Autor: Michael Schuliga, Shenna Y. Langenbach, Trudi Harris, Christine R. Keenan, Asres Berhan, Simon G. Royce, Alastair G. Stewart
Rok vydání: 2015
Předmět:
Zdroj: American journal of respiratory cell and molecular biology. 54(2)
ISSN: 1535-4989
Popis: During asthma exacerbation, plasma circulating coagulant factor X (FX) enters the inflamed airways and is activated (FXa). FXa may have an important role in asthma, being involved in thrombin activation and an agonist of protease-activated receptor-1 (PAR-1). Extracellular annexin A2 and integrins are also implicated in PAR-1 signaling. In this study, the potential role of PAR-1 in mediating the effects of FXa on human airway smooth muscle (ASM) cell cytokine production and proliferation was investigated. FXa (5-50 nM), but not FX, stimulated increases in ASM IL-6 production and cell number after 24- and 48-hour incubation, respectively (P < 0.05; n = 5). FXa (15 nM) also stimulated increases in the levels of mRNA for cytokines (IL-6), cell cycle-related protein (cyclin D1), and proremodeling proteins (FGF-2, PDGF-B, CTGF, SM22, and PAI-1) after 3-hour incubation (P
Databáze: OpenAIRE