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The inflammasome and caspase-1 involvement in systemic sclerosis fibroblasts mediates fibrosis and myofibroblast differentiation (44.33)
Journal article   Peer reviewed

The inflammasome and caspase-1 involvement in systemic sclerosis fibroblasts mediates fibrosis and myofibroblast differentiation (44.33)

Carol Artlett, Sihem Sassi-Gaha, Judy Rieger, Alina Boesteanu, Carol Feghali-Bostwick and Peter Katsikis
The Journal of immunology (1950), v 186(1_Supplement), pp 44-44.33
01 Apr 2011
DOI: https://doi.org/10.4049/jimmunol.186.Supp.44.33

Abstract

Abstract Systemic sclerosis (SSc) is a chronic idiopathic disease of unknown etiology that is characterized by fibrosis of the skin and visceral organs mediated by activated myofibroblasts. The recently identified inflammasomes are cytosolic receptors that tightly regulate the activity of caspase-1 and downstream signaling molecules such as IL-1β and IL-18. The NLRP3 inflammasome has been implicated in the development of idiopathic pulmonary fibrosis; however the role of the inflammasome has not been studied in SSc dermal or lung fibrosis. We identified increased expression of 40 genes associated with the inflammasome or downstream signaling molecules in SSc fibroblasts. Inhibition of caspase-1 in SSc dermal and lung fibroblasts abrogated secretion of collagens, and IL-1β and IL-18. In fibrotic SSc lesions, persistently activated fibroblasts called myofibroblasts mediate the excessive secretion of collagen and other extracellular matrix proteins in both the dermis and visceral organs. We observed decreased expression of the myofibroblast protein α-smooth muscle actin in SSc dermal fibroblasts treated with the caspase-1 inhibitor. NLRP3-/- and ASC-/- mice were resistant to bleomycin-induced skin fibrosis suggesting a key role for the inflammasome in in vivo dermal fibrosis. We report that innate immune signaling contributes to SSc fibrosis via the activation of the inflammasome and caspase-1 and suggest that inflammasome activation may play an important role in the pathogenesis of SSc.

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