Home
|
Inbox
|
Search
|
View Abstract
Sex-Specific MicroRNA Expression in Ozone-Induced Lung Inflammation
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A7557 - Sex-Specific MicroRNA Expression in Ozone-Induced Lung Inflammation
Author Block: N. Fuentes Ortiz, A. Roy, N. Cabello, P. Silveyra; Pediatrics, Penn State College of Medicine, Hershey, PA, United States.
Rationale: Sex differences in the incidence and prognosis of respiratory diseases have been reported. Studies have shown that women are at increased risk of adverse health outcomes from air pollution than men, but the specific mechanisms behind these differences have not been well studied. MicroRNAs (miRNAs) are environmentally sensitive posttranscriptional regulators of gene expression that may mediate the damaging effects of inhaled pollutants in the lung. Based on our preliminary data in which we found sex differences in the expression of lung inflammatory markers in response to ozone exposure, we hypothesized that sex-specific miRNA expression can mediate gender-specific immune responses to ozone via modulation of gene expression.
Methods: Male and female adult C57BL/6J mice were exposed to ozone (2ppm, 3h) or filtered air (FA, control). Four hours after exposure, whole lungs were harvested and RNA was extracted. We used PCR arrays to characterize sex-differences in the expression of 84 miRNAs predicted to regulate the expression of inflammatory genes in lung tissue. Results were analyzed with the limma package on R. Using false discovery rate adjustment for multiple comparisons and in silico ingenuity pathway analysis (IPA), we identified differentially expressed miRNAs in males and females in response to ozone, predicted target genes, and associated biological pathways.
Results: We identified basal and ozone-induced sex differences in lung miRNA expression. Exposure to ozone differentially affected lung miRNA expression in male and female mice. In silico analysis revealed that the top molecular functions associated with differentially expressed miRNAs in males vs. females exposed to ozone were linked to cell cycle, cellular development, and cellular growth and proliferation, which are important pathways in the lung inflammatory response. Moreover, the top associated network functions included organismal and tissue development, humoral immune response, and reproductive system development and function. Several differentially expressed miRNAs were also involved in inflammation (miR-130a-3p, miR-17-5p, miR-291a-3p and miR-338-5p), and their predicted targets are key regulators of the immune response (IL-6, SMAD2/3 and TMEM9).
Conclusions: We conclude that both sex and hormonal status can influence lung miRNA expression in response to ozone exposure. We postulate that sex-specific miRNA regulation of inflammatory gene expression may mediate differential health outcomes in men and women exposed to air pollution.
Author Block: N. Fuentes Ortiz, A. Roy, N. Cabello, P. Silveyra; Pediatrics, Penn State College of Medicine, Hershey, PA, United States.
Rationale: Sex differences in the incidence and prognosis of respiratory diseases have been reported. Studies have shown that women are at increased risk of adverse health outcomes from air pollution than men, but the specific mechanisms behind these differences have not been well studied. MicroRNAs (miRNAs) are environmentally sensitive posttranscriptional regulators of gene expression that may mediate the damaging effects of inhaled pollutants in the lung. Based on our preliminary data in which we found sex differences in the expression of lung inflammatory markers in response to ozone exposure, we hypothesized that sex-specific miRNA expression can mediate gender-specific immune responses to ozone via modulation of gene expression.
Methods: Male and female adult C57BL/6J mice were exposed to ozone (2ppm, 3h) or filtered air (FA, control). Four hours after exposure, whole lungs were harvested and RNA was extracted. We used PCR arrays to characterize sex-differences in the expression of 84 miRNAs predicted to regulate the expression of inflammatory genes in lung tissue. Results were analyzed with the limma package on R. Using false discovery rate adjustment for multiple comparisons and in silico ingenuity pathway analysis (IPA), we identified differentially expressed miRNAs in males and females in response to ozone, predicted target genes, and associated biological pathways.
Results: We identified basal and ozone-induced sex differences in lung miRNA expression. Exposure to ozone differentially affected lung miRNA expression in male and female mice. In silico analysis revealed that the top molecular functions associated with differentially expressed miRNAs in males vs. females exposed to ozone were linked to cell cycle, cellular development, and cellular growth and proliferation, which are important pathways in the lung inflammatory response. Moreover, the top associated network functions included organismal and tissue development, humoral immune response, and reproductive system development and function. Several differentially expressed miRNAs were also involved in inflammation (miR-130a-3p, miR-17-5p, miR-291a-3p and miR-338-5p), and their predicted targets are key regulators of the immune response (IL-6, SMAD2/3 and TMEM9).
Conclusions: We conclude that both sex and hormonal status can influence lung miRNA expression in response to ozone exposure. We postulate that sex-specific miRNA regulation of inflammatory gene expression may mediate differential health outcomes in men and women exposed to air pollution.
|
Home
|
Inbox
|
Search
|