AI Article Synopsis
- Exposure to particulate matter (PM) triggers mitochondrial dysfunction and lung inflammation, with COX-2 playing a crucial role in these processes.
- The study investigated how glucocorticoid receptors (GRs) suppress PM-induced COX-2 expression in A549 cells, discovering that this suppression is counteracted by the GR antagonist RU486.
- Results showed that reactive oxygen species (ROS) contribute to COX-2 induction during PM exposure, and glucocorticoids help reverse mitochondrial damage while enhancing the relationship between GR and Bcl-2, suggesting new potential therapeutic targets for inflammation related to PM.
Article Abstract
Exposure to particulate matter (PM) causes mitochondrial dysfunction and lung inflammation. The cyclooxygenase-2 (COX-2) pathway is important for inflammation and mitochondrial function. However, the mechanisms by which glucocorticoid receptors (GRs) suppress COX-2 expression during PM exposure have not been elucidated yet. Hence, we examined the mechanisms underlying the dexamethasone-mediated suppression of the PM-induced COX-2/prostaglandin E2 (PGE2) pathway in A549 cells. The PM-induced increase in COX-2 protein, mRNA, and promoter activity was suppressed by glucocorticoids; this effect of glucocorticoids was antagonized by the GR antagonist RU486. COX-2 induction was correlated with the ability of PM to increase reactive oxygen species (ROS) levels. Consistent with this, antioxidant treatment significantly abolished COX-2 induction, suggesting that ROS is involved in PM-mediated COX-2 induction. We also observed a low mitochondrial membrane potential in PM-treated A549 cells, which was reversed by dexamethasone. Moreover, glucocorticoids significantly enhanced Bcl-2/GR complex formation in PM-treated A549 cells. Glucocorticoids regulate the PM-exposed induction of COX-2 expression and mitochondrial dysfunction and increase the interaction between GR and Bcl-2. These findings suggest that the COX-2/PGE2 pathway and the interaction between GR and Bcl-2 are potential key therapeutic targets for the suppression of inflammation under PM exposure.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622527 | PMC |
| http://dx.doi.org/10.1038/s41598-023-46257-y | DOI Listing |
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