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Title: | Pirfenidone: Molecular mechanisms and potential clinical applications in lung disease. | Authors: | Ruwanpura S.M.;Bardin P.G.;Thomas B.J. | Monash Health Department(s): | Respiratory and Sleep Medicine | Institution: | (Ruwanpura, Thomas, Bardin) Monash Lung and Sleep, Monash Health, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia (Thomas, Bardin) Hudson Institute of Medical Research, Clayton, VIC, Australia | Issue Date: | 30-Jun-2020 | Copyright year: | 2020 | Publisher: | American Thoracic Society (E-mail: malexander@thoracic.org) | Place of publication: | United States | Publication information: | American Journal of Respiratory Cell and Molecular Biology. 62 (4) (pp 413-422), 2020. Date of Publication: 2020. | Journal: | American Journal of Respiratory Cell and Molecular Biology | Abstract: | Pirfenidone (PFD) is a pharmacological compound with therapeutic efficacy in idiopathic pulmonary fibrosis. It has been chiefly characterized as an antifibrotic agent, although it was initially developed as an antiinflammatory compound because of its ability to diminish the accumulation of inflammatory cells and cytokines. Despite recent studies that have elucidated key mechanisms, the precise molecular activities of PFD remain incompletely understood. PFD modulates fibrogenic growth factors, thereby attenuating fibroblast proliferation, myofibroblast differentiation, collagen and fibronectin synthesis, and deposition of extracellular matrix. This effect is mediated by suppression of TGF-b1 (transforming growth factor-b1) and other growth factors. Here, we appraise the impact of PFD on TGF-b1 production and its downstream pathways. Accumulating evidence indicates that PFD also downregulates inflammatory pathways and therefore has considerable potential as a viable and innovative antiinflammatory compound. We examine the effects of PFD on inflammatory cells and the production of pro- and antiinflammatory cytokines in the lung. In this context, recent evidence that PFD can target inflammasome pathways and ensuing lung inflammation is highlighted. Finally, the antioxidant properties of PFD, such as its ability to inhibit redox reactions and regulate oxidative stress-related genes and enzymes, are detailed. In summary, this narrative review examines molecular mechanisms underpinning PFD and its recognized benefits in lung fibrosis. We highlight preclinical data that demonstrate the potential of PFD as a nonsteroidal antiinflammatory agent and outline areas for future research.Copyright © 2020 by the American Thoracic Society. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1165/rcmb.2019-0328TR | PubMed URL: | 31967851 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31967851] | ISSN: | 1044-1549 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/29264 | Type: | Review | Subjects: | antiinflammatory activity drug effect human inflammatory cell lung disease/dt [Drug Therapy] *lung fibrosis/dt [Drug Therapy] antifibrotic activity *pirfenidone/pd [Pharmacology] transforming growth factor beta1/ec [Endogenous Compound] nonhuman pharmacology review cytokine/ec [Endogenous Compound] inflammasome/ec [Endogenous Compound] *pirfenidone/dt [Drug Therapy] antiinflammatory activity drug effect inflammatory cell lung disease lung fibrosis antifibrotic activity pirfenidone transforming growth factor beta1 pharmacology cytokine inflammasome pirfenidone Review *lung fibrosis / *drug therapy lung disease / drug therapy inflammatory cell nonhuman drug effect human pharmacology antiinflammatory activity antifibrotic activity |
Type of Clinical Study or Trial: | Review article (e.g. literature review, narrative review) |
Appears in Collections: | Articles |
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