title: Mast cell chymase: an indispensable instrument in the pathological symphony of idiopathic pulmonary fibrosis?
abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease with no known etiology and treatment options. The hallmarks of the histopathology, which is characteristic of usual interstitial pneumonia (UIP) pattern, include interstitial fibrosis, honeycomb changes and fibroblast foci that develop owing to fibroblast proliferation and excessive matrix deposition. Although the complete pathomechanism is not yet understood, several molecular culprits, including transforming growth factor (TGF)-β, Angiotensin (Ang) II, endothelin (ET)-1, matrix metalloproteinases (MMPs) and cytokines have been identified. IPF is increasingly believed to be an epithelial-driven disease; however, the literature does support an implication of altered immune response and inflammatory processes in the onset or progression of the disease. Mast cells (MCs) are multifunctional tissue resident cells involved in the inflammatory and immune response. An increasing body of evidence suggests a role of MCs and their mediator chymase in the pathology of IPF. With regard to the underlying mechanisms, it is conceivable that MC chymase may function via activation or processing of factors such as proteases, cytokines and growth factors. In this review, we will discuss how MC chymase is linked to and can potentially contribute to the development of IPF. Moreover, the findings from animal model studies will be discussed to highlight the chymase inhibitors as a promising strategy for the treatment of pulmonary fibrosis.
authors: Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research, Giessen, Germany.
authors: Djuro
authors: D
authors: Kosanovic
authors: Bhola Kumar
authors: BK
authors: Dahal
authors: Malgorzata
authors: M
authors: Wygrecka
authors: Irwin
authors: I
authors: Reiss
authors: Andreas
authors: A
authors: Günther
authors: Hossein Ardeschir
authors: HA
authors: Ghofrani
authors: Norbert
authors: N
authors: Weissmann
authors: Friedrich
authors: F
authors: Grimminger
authors: Werner
authors: W
authors: Seeger
authors: Ralph Theo
authors: RT
authors: Schermuly
authors: Gamal-Andre
authors: GA
authors: Banat
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D053818:Chymases / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology; D051379:Mice
chemical_list: D015415:Biomarkers; D053818:Chymases