{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:15:44Z","timestamp":1793898944806,"version":"4.8.0"},"reference-count":119,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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-\u03b21 (transforming growth factor-\u03b21) and other growth factors. Here, we appraise the impact of PFD on TGF-\u03b21 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\u2013related 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.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0328tr","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T15:57:11Z","timestamp":1579708631000},"page":"413-422","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":295,"title":["Pirfenidone: Molecular Mechanisms and Potential Clinical Applications in Lung Disease"],"prefix":"10.1093","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4074-2012","authenticated-orcid":false,"given":"Saleela M.","family":"Ruwanpura","sequence":"first","affiliation":[{"name":"Monash Lung and Sleep, Monash Health, Monash Medical Centre, Clayton, Victoria, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda J.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Monash Lung and Sleep, Monash Health, Monash Medical Centre, Clayton, Victoria, Australia; and"},{"name":"Hudson Institute of Medical Research, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip G.","family":"Bardin","sequence":"additional","affiliation":[{"name":"Monash Lung and Sleep, Monash Health, Monash Medical Centre, Clayton, Victoria, Australia; and"},{"name":"Hudson Institute of Medical Research, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,1]]},"reference":[{"key":"2026021100415023200_bib1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1513\/AnnalsATS.201809-604CME","article-title":"2018 clinical practice guideline summary for clinicians: diagnosis of idiopathic pulmonary fibrosis","volume":"16","author":"Thomson","year":"2019","journal-title":"Ann Am Thorac 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