The Role of Estrogen Receptor β in PM2.5 Organic Extract-Induced Pulmonary Inflammation in Female and Male Mice

Abstract

Automobile exhaust is one of the main sources of PM2.5 in urban areas, and traffic-originated PM2.5 organic extract (Po) can promote inflammation in different organs, especially in the lung. In addition, sex differences were reported in many inflammatory diseases, but the triggering factors of sex differences in inflammatory responses are still unclear. In this study, we investigated the effects of Po exposure on pulmonary inflammatory responses and evaluated the role of sex in this process. Mice were exposed to 100 µg/m3 Po for 12 weeks by an inhalation exposure system in a polycarbonate chamber. In Po-exposed mice, the lung histopathological analysis shown obvious inflammation, the cell numbers in bronchoalveolar lavage fluid (BALF) were significantly increased, and most inflammatory cytokines in BALF were upregulated. Factorial analysis of variance was carried out to investigate the interaction between sex and Po exposure in these effects. The results shown that the increase of inflammatory cell numbers and the fluctuation of cytokine levels (TNF-α, IL-5, and GRO/KC) in BALF induced by Po were significantly different between female and male mice. Notably, these differences were diminished while Po-exposed mice were injected with PHTPP, an ERβ antagonist (1 mg/kg, i.p.). We hypothesized that Po-induced inflammatory responses were different between female and male mice, and ERβ was involved in these processes. To our knowledge, this is the first investigation about the role of sex in Po-induced adverse effects. This study provided a theoretical basis for understanding the sex differences in the adverse effects of environmental pollutants.