Resolvins attenuate inflammation and promote resolution in cigarette smoke-exposed human macrophages

Am J Physiol Lung Cell Mol Physiol. 2015 Oct 15;309(8):L888-901. doi: 10.1152/ajplung.00125.2015. Epub 2015 Aug 21.


Inflammation is a protective response to injury, but it can become chronic, leading to tissue damage and disease. Cigarette smoke causes multiple inflammatory diseases, which account for thousands of deaths and cost billions of dollars annually. Cigarette smoke disrupts the function of immune cells, such as macrophages, by prolonging inflammatory signaling, promoting oxidative stress, and impairing phagocytosis, contributing to increased incidence of infections. Recently, new families of lipid-derived mediators, "specialized proresolving mediators" (SPMs), were identified. SPMs play a critical role in the active resolution of inflammation by counterregulating proinflammatory signaling and promoting resolution pathways. We have identified dysregulated concentrations of lipid mediators in exhaled breath condensate, bronchoalveolar lavage fluid, and serum from patients with chronic obstructive pulmonary disease (COPD). In human alveolar macrophages from COPD and non-COPD patients, D-series resolvins decreased inflammatory cytokines and enhanced phagocytosis. To further investigate the actions of resolvins on human cells, macrophages were differentiated from human blood monocytes and treated with D-series resolvins and then exposed to cigarette smoke extract. Resolvins significantly suppressed macrophage production of proinflammatory cytokines, enzymes, and lipid mediators. Resolvins also increased anti-inflammatory cytokines, promoted an M2 macrophage phenotype, and restored cigarette smoke-induced defects in phagocytosis, highlighting the proresolving functions of these molecules. These actions were receptor-dependent and involved modulation of canonical and noncanonical NF-κB expression, with the first evidence for SPM action on alternative NF-κB signaling. These data show that resolvins act on human macrophages to attenuate cigarette smoke-induced inflammatory effects through proresolving mechanisms and provide new evidence of the therapeutic potential of SPMs.

Keywords: chronic obstructive pulmonary disease; cigarette smoke; macrophage; resolvin; specialized proresolving mediators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / biosynthesis
  • Docosahexaenoic Acids / pharmacology*
  • Humans
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism
  • Lipid Metabolism / drug effects
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / pathology
  • Macrophages, Alveolar / physiology
  • Oxidative Stress / drug effects
  • Phagocytosis / drug effects
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Signal Transduction / drug effects
  • Smoke / adverse effects
  • Smoking / adverse effects*


  • Cytokines
  • Inflammation Mediators
  • Smoke
  • resolvin D1
  • Docosahexaenoic Acids