Quenching the fires: Pro-resolving mediators, air pollution, and smoking

Abstract

Exposure to air pollution and other environmental inhalation hazards, such as occupational exposures to dusts and fumes, aeroallergens, and tobacco smoke, is a significant cause of chronic lung inflammation leading to respiratory disease. It is now recognized that resolution of inflammation is an active process controlled by a novel family of small lipid mediators termed "specialized pro-resolving mediators" or SPMs, derived mainly from dietary omega-3 polyunsaturated fatty acids. Chronic inflammation results from an imbalance between pro-inflammatory and pro-resolution pathways. Research is ongoing to develop SPMs, and the pro-resolution pathway more generally, as a novel therapeutic approach to diseases characterized by chronic inflammation. Here, we will review evidence that the resolution pathway is dysregulated in chronic lung inflammatory diseases, and that SPMs and related molecules have exciting therapeutic potential to reverse or prevent chronic lung inflammation, with a focus on lung inflammation due to inhalation of environmental hazards including urban particulate matter, organic dusts and tobacco smoke.

Keywords: Air pollution; COPD; Chronic inflammation; Cigarette smoking; Pro-resolving mediators; SPMs.

Figure 1.

Diagram of the synthetic pathways for the major classes of SPMs, with selected enzymatic processing steps, final products and degradation pathways. Stars indicate sites at which the aspirin-triggered epimers differ from the standard compound. Abbreviations: (Ac)Cox2, acetylated Cox2; CYP, Cytochrome P450 enzymes; EOR; epoxide oxoreductase; HDHA, hydroxydocosahexaenoic acid; HEPE, hydroxyeicosapentaenoic acid; HETE, hydroxyeicosatetraenoic acid; sHE, soluble epoxide hydrolase. Other abbreviations as defined in the main text.

Figure 1.

Diagram of the synthetic pathways for the major classes of SPMs, with selected enzymatic processing steps, final products and degradation pathways. Stars indicate sites at which the aspirin-triggered epimers differ from the standard compound. Abbreviations: (Ac)Cox2, acetylated Cox2; CYP, Cytochrome P450 enzymes; EOR; epoxide oxoreductase; HDHA, hydroxydocosahexaenoic acid; HEPE, hydroxyeicosapentaenoic acid; HETE, hydroxyeicosatetraenoic acid; sHE, soluble epoxide hydrolase. Other abbreviations as defined in the main text.

Figure 2.. RvD1 is decreased in COPD patients.

Panels A and B: RvD1 was measured in bronchoalveolar lavage fluid (BAL) and serum from non-smokers without COPD and from COPD patients by EIA as previously reported (Croasdell, et al., 2015). Panel C: Levels of eicosanoid oxidoreductase (EOR), an enzyme that degrades and inactivates RvD1, were measured in lung tissue from non-smoking donors or COPD patients, as previously reported (Hsiao, et al., 2015).