Sex differences in the expression of lung inflammatory mediators in response to ozone

Abstract

Sex differences in the incidence of respiratory diseases have been reported. Women are more susceptible to inflammatory lung disease induced by air pollution and show worse adverse pulmonary health outcomes than men. However, the mechanisms underlying these differences remain unknown. In the present study, we hypothesized that sex differences in the expression of lung inflammatory mediators affect sex-specific immune responses to environmental toxicants. We focused on the effects of ground-level ozone, a major air pollutant, in the expression and regulation of lung immunity genes. We exposed adult male and female mice to 2 ppm of ozone or filtered air (control) for 3 h. We compared mRNA levels of 84 inflammatory genes in lungs harvested 4 h postexposure using a PCR array. We also evaluated changes in lung histology and bronchoalveolar lavage fluid cell counts and protein content at 24 and 72 h postexposure. Our results revealed sex differences in lung inflammation triggered by ozone exposure and in the expression of genes involved in acute phase and inflammatory responses. Major sex differences were found in the expression of neutrophil-attracting chemokines (Ccl20, Cxcl5, and Cxcl2), the proinflammatory cytokine interleukin-6, and oxidative stress-related enzymes (Ptgs2, Nos2). In addition, the phosphorylation of STAT3, known to mediate IL-6-related immune responses, was significantly higher in ozone-exposed mice. Together, our observations suggest that a differential regulation of the lung immune response could be implicated in the observed increased susceptibility to adverse health effects from ozone observed in women vs. men.

Spatiotemporal Patterns of Ozone and Cardiovascular and Respiratory Disease Mortalities Due to Ozone in Shenzhen

“…The elderly group (65 years and older) showed the highest cardio-respiratory mortality risk with an ER percentage of 1.59 (1.35-1.83) per daily 8-h maximum ozone concentration increasing by 10 µg/m 3 in this study. From a gender perspective, animal experimental research and meta-analysis have shown that women were more susceptible to inflammatory lung disease induced by air pollution and show worse adverse pulmonary health outcomes than men [36,37]. By contrast, our research found a more obvious negative association between ozone exposure and cardiovascular and respiratory mortality among males than females.…”

“…Because of largely existing pre-conditions or deprived immune systems, elderly people are more vulnerable to ozone exposure than the younger generation [36]. The elderly group (65 years and older) showed the highest cardio-respiratory mortality risk with an ER percentage of 1.59 (1.35-1.83) per daily 8-h maximum ozone concentration increasing by 10 µg/m 3 in this study.…”

“…The health risk caused by ozone exposure is influenced by the emissions of precursor chemical species, meteorology and population themselves [12,14,36,37]. Precursor chemicals mainly are methane (CH 4 ) and carbon monoxide (CO), which, with the emissions of nitrogen oxides (NO x = NO + NO 2 ), contribute to a general hemispheric 'background' of ozone.…”

Modulation of the lung inflammatory response to ozone by the estrous cycle

“…We recovered BAL cells in 2.5 mL of DPBS with 1 mmol/L EDTA and analyzed as described in Cabello et al. (). We determined lipocalin‐2/NGAL levels by ELISA (R&D Systems, Minneapolis MN, kit #MLCN20) in 50 μ L of BAL.…”

“…Previously, we reported sex differences in both gene expression and miRNA signatures in response to ozone exposure using mouse models (Cabello et al. ; Fuentes et al. ).…”