Proteases in agricultural dust induce lung inflammation through PAR-1 and PAR-2 activation (original) (raw)

American journal of physiology. Lung cellular and molecular physiology, 2015

Abstract

Workers exposed to aerosolized dust present in concentrated animal feeding operations (CAFOs) are susceptible to inflammatory lung diseases such as COPD. Extracts of dust collected from hog CAFOs (HDE) are potent stimulators of lung inflammatory responses in several model systems. The observation that HDE contains active proteases prompted the present study, which evaluated the role of CAFO dust proteases in lung inflammatory processes and tested whether protease-activated receptors (PARs) are involved in the signaling pathway for these events. We hypothesized that the damaging proinflammatory effect of HDE is due partly to proteolytic activation of PARs, and inhibiting HDE proteases or disrupting PAR activation would attenuate HDE-mediated inflammatory indices in bronchial epithelial cells (BECs), mouse lung slices in vitro, and in a murine in vivo exposure model. Human BECs and mouse lung slice cultures stimulated with 5% HDE released significantly more of each of the cytokines me...

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