Is there a role for specialized pro-resolving mediators in pulmonary fibrosis?

• Published in: Pharmacology & therapeutics (Oxford) 2023-07, Vol.247, p.108460-108460, Article 108460
• Main Authors: Thatcher, Thomas H., Freeberg, Margaret A.T., Myo, Yu Par Aung, Sime, Patricia J.
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; Fibroblast; Fibrosis; Idiopathic pulmonary fibrosis; Inflammation - drug therapy; Inflammation Mediators - metabolism; Interstitial lung disease; Lipids; Lung - metabolism; Pro-resolving mediators; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Sarcoidosis; Scleroderma; SPMs
• ISSN: 0163-7258; 1879-016X; 1879-016X
• DOI: 10.1016/j.pharmthera.2023.108460

Pulmonary fibrotic diseases are characterized by proliferation of lung fibroblasts and myofibroblasts and excessive deposition of extracellular matrix proteins. Depending on the specific form of lung fibrosis, there can be progressive scarring of the lung, leading in some cases to respiratory failure and/or death. Recent and ongoing research has demonstrated that resolution of inflammation is an active process regulated by families of small bioactive lipid mediators termed “specialized pro-resolving mediators.” While there are many reports of beneficial effects of SPMs in animal and cell culture models of acute and chronic inflammatory and immune diseases, there have been fewer reports investigating SPMs and fibrosis, especially pulmonary fibrosis. Here, we will review evidence that resolution pathways are impaired in interstitial lung disease, and that SPMs and other similar bioactive lipid mediators can inhibit fibroblast proliferation, myofibroblast differentiation, and accumulation of excess extracellular matrix in cell culture and animal models of pulmonary fibrosis, and we will consider future therapeutic implications of SPMs in fibrosis.