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Sex Differences in the Lung Inflammatory Response to Acute Ozone Exposure

Ozone reacts with biological molecules and causes lung inflammation, injury, and other health effects. In order to prevent oxidant‐induced lung injury, synthesis of cytokines and inflammatory mediators, and activation of transcription factors in the lung and immune cells are critical. Research has shown that the incidence of respiratory diseases varies according to gender. In this work, we investigated sex differences in the lung innate immune response to acute ozone exposure. For this, adult male and female mice were exposed to ozone (2ppm) or filtered air (FA) for 3 hours (n=8/group). Animals were sacrificed 4 hours post‐exposure, and lungs were harvested. The expression of cytokines, chemokines, and transcription factors was analyzed by Real Time PCR and normalized to 18S. We found that ozone exposure significantly increased expression of the chemokines MIP‐1 and MIP‐2, and the cytokine IL‐6, in male and female mice. Ozone treated females showed considerably higher expression of MIP‐1, MIP‐2, IL1α, and IL‐6 as compared to females exposed to FA (p<0.05). Likewise, ozone treated males showed higher levels of MIP‐2 and IL‐6 as compared to FA treated males (p<0.005). When compared to males, ozone treated females expressed higher levels of MIP‐1, MIP‐2, IL1α, and IL‐6 (p<0.05). Expression of the transcription factor STAT3 was also increased in females in response to ozone (p<0.05). Our results indicate that sex differences exist in lung gene expression of innate immunity molecules in response to acute ozone exposure. 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 in women vs. men (Supported by BIRCWH K12HD055882).