Sex differences in lung miRNA‐712 expression and inflammatory cytokines in a mouse model of asthma and air pollution exposure

Background MicroRNAs (miRNAs) are short RNAs (18–22 nucleotides) that play a critical role in post‐transcriptional gene regulation. Specifically miRNA 712‐5p has been shown to play a major role in the regulation of inflammatory cytokine expression, which is one of the hallmarks of asthma. Asthma has been shown to afflict more adult females than males. Asthmatic females are also more susceptible to air pollution exposure, which leads to higher rates of respiratory disease. The hypothesis of our work is that differential expression of specific miRNAs that regulate inflammatory cytokine expression in the male and female lung upon exposure to an air pollutant could contribute to the mechanisms responsible for the higher susceptibility of females to respiratory disease. Methods To test this hypothesis, we developed an asthma model in which male and female C57BL/6 mice were sensitized with house dust mite (HDM) or phosphate buffer saline (PBS) for five‐weeks, followed by a three‐hour ozone or filtered air exposure challenge to induce inflammation. Following exposure, lungs were harvested and total RNA was extracted and converted to cDNA. Relative miRNA expression linked to inflammatory cytokine production was measured by real‐time PCR and normalized with U6. Cytokine gene expression was also determined by real time PCR. Results Preliminary results show that there are sex‐specific differences in miR‐712 expression as well as inflammatory cytokine gene expression in asthmatic mice. The data shows that both males and females express higher amount of miR‐712 upon sensitization to HDM compared to PBS and that ozone also increases the levels of miR‐712 expressed in both sexes. Upon exposure to ozone, females sensitized with PBS express higher amounts of miR‐712 than males. However, males sensitized with HDM and exposed to ozone express more miR‐712 than females. Conclusion MiR‐712 is differentially expressed between asthmatic males and females following exposure to a pollutant. Since, miR‐712 is known to regulate inflammation, the differential expression of this miRNA could account for the increased susceptibility of asthmatic adult females to pollution. The results of this study could help us to further understand the sex‐specific mechanisms of asthma, and develop novel therapies. Support or Funding Information NIH (HL133520, HL141618) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .