Role of Estrogen on Alveolar Macrophage Polarization in Response to Particulate Matter Exposure

Abstract

BackgroundLung diseases affect more than 500 million people worldwide. Exposure to air pollutants such as particulate matter (PM) contributes significantly to lung disease, especially in women, indicating an intersection of air pollution and sex hormones in lung disease outcomes. Studies have been performed on the effects of estrogens on lung immunity, particularly in alveolar macrophages (AM). AMs provide one of the first lines of defense in the airways and are important mediators of inflammation. However, the mechanisms by which estrogens control the immune response to PM exposure remain unclear. Here, we hypothesized that PM exposure triggers AM polarization to the pro‐inflammatory (M1) macrophage phenotype in a sex‐dependent matter, and that this process is mediated by estrogens in female cells.MethodsWe tested this hypothesis by exposing male (RAW264.7, BALB/c) and female mouse AMs (J774A.1, BALB/c) to a synthetic PM preparation in the presence or absence of estrogen agonists/antagonists. Cell viability and cytotoxicity were measured at 8h to determine PM dose‐responses. Cells were then stimulated with LPS or IL‐4, which have been described as mediators of AM polarization. The polarization phenotype, determined by expression of specific markers (iNOS, Arg1), was evaluated by quantitative real‐time PCR.ResultsOur results demonstrate that estrogen treatment decreases iNOS expression and increases Arg1 expression, impairing the LPS‐induced pro‐inflammatory phase and triggering resolution of inflammation in RAW 264.7 cells. In addition, induction of AM polarization towards different phenotypes not only was altered by PM and estrogen treatment, but also depended on the sex of the cell. Interestingly, PM treatment led to decreased expression of estrogen receptors when compared to the non‐PM treated cells.ConclusionsWe conclude that estrogens regulate the immune response to PM in a sex‐dependent manner. These findings may be relevant to elucidate the transcriptional mechanisms involved in the sex‐specific inflammatory response and particularly for the identification of novel hormone receptor modulators efficacious in the prevention or mitigation of chronic inflammation in men and women.Support or Funding InformationThis research was supported by funding from NIH K01HL133520, the Center for Research on Women and Newborn Health and the American Physiological Society Porter Physiology Development Program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.