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Review
. 2023 Jul:247:108460.
doi: 10.1016/j.pharmthera.2023.108460. Epub 2023 May 26.

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

Thomas H Thatcher  1 , Margaret A T Freeberg  1 , Yu Par Aung Myo  2 , Patricia J Sime  3
Affiliations
Review

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

Thomas H Thatcher et al. Pharmacol Ther. 2023 Jul.

Abstract

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.

Keywords: Fibroblast; Idiopathic pulmonary fibrosis; Interstitial lung disease; Pro-resolving mediators; SPMs; Sarcoidosis; Scleroderma.

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Conflict of interest statement

Declaration of Competing Interest Dr. Sime is a paid consultant for Boehringer Ingelheim, UCB Pharma S.A., and Three Lakes Foundation. She serves on the board for the American Thoracic Society, the scientific council of the Parker Francis Foundation, an advisory board for Galecto, and the medical scientific advisory committee for the Pulmonary Fibrosis Foundation. She receives grant funding from the NIH. Dr. Sime holds patents related to fibrosis. The other authors have no financial interests to disclose.

Figures

Figure 1.
Figure 1.. Radiologic and histologic features of Idiopathic Pulmonary Fibrosis (IPF).
A. High resolution CT scan from patient with IPF. Yellow arrows point to honeycombing and fibrotic features. B-D. H&E stained sections of normal (B) and IPF (C, D) lung tissue. In C, the black arrow indicates fibrotic tissue while the white area indicates adjacent uninvolved parenchyma. In D, ff indicates fibroblastic foci, a hallmark feature of IPF.
Figure 2.
Figure 2.. Diagram of synthetic pathways for the major classes of SPMs.
SPMs are derived from Omega-3 and –6 polyunsaturated fatty acids through a series of enzymatic reactions. Pro-resolving mediators consist of Resolvins (Rv-), Maresins (MaR-), Protectins (PD-), and Lipoxins (LX-). Pro-inflammatory mediators Prostaglandins and Leukotrienes are derived from Arachidonic Acid. Abbreviations are defined in the main text and abbreviations table. Created with Biorender.com.
Figure 3.
Figure 3.. SPM receptor network.
Diagram of the GPCR signaling network for SPMs. Multiple SPMs (left) can bind the same receptors (right). Green indicates pro-resolving mediators, and red indicates pro-inflammatory mediators. Abbreviations are defined in the main text and abbreviations table. Created with Biorender.com.
See this image and copyright information in PMC

References

    1. Abdalla M, Sabbineni H, Prakash R, Ergul A, Fagan SC, & Somanath PR (2015). The Akt inhibitor, triciribine, ameliorates chronic hypoxia-induced vascular pruning and TGFbeta-induced pulmonary fibrosis. Br J Pharmacol, 172, 4173–4188. - PMC - PubMed
    1. Abreu SC, Lopes-Pacheco M, da Silva AL, Xisto DG, de Oliveira TB, Kitoko JZ, de Castro LL, Amorim NR, Martins V, Silva LHA, Goncalves-de-Albuquerque CF, de Castro Faria-Neto HC, Olsen PC, Weiss DJ, Morales MM, Diaz BL, & Rocco PRM (2018). Eicosapentaenoic Acid Enhances the Effects of Mesenchymal Stromal Cell Therapy in Experimental Allergic Asthma. Front Immunol, 9, 1147. - PMC - PubMed
    1. Akagi D, Chen M, Toy R, Chatterjee A, & Conte MS (2015). Systemic delivery of proresolving lipid mediators resolvin D2 and maresin 1 attenuates intimal hyperplasia in mice. FASEB J, 29, 2504–2513. - PMC - PubMed
    1. Artiach G, Carracedo M, Claria J, Laguna-Fernandez A, & Back M (2018). Opposing Effects on Vascular Smooth Muscle Cell Proliferation and Macrophage-induced Inflammation Reveal a Protective Role for the Proresolving Lipid Mediator Receptor ChemR23 in Intimal Hyperplasia. Front Pharmacol, 9, 1327. - PMC - PubMed
    1. Ashley SL, Wilke CA, Kim KK, & Moore BB (2017). Periostin regulates fibrocyte function to promote myofibroblast differentiation and lung fibrosis. Mucosal Immunol, 10, 341–351. - PMC - PubMed

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