FIGURE 9.

Proposed effects of MRSA on CYP1A1 expression and lung EC function. This schema summarizes observations from the current study in which MRSA induces CYP1A1 expression in lung EC and causes lung endothelial barrier disruption and inflammation. MRSA increases the acetylation of histone H3 at lysine K9 (H3K9) within the CYP1A1 promoter region, enhancing its transcription and subsequent expression. The dashed line indicates that the mechanism by which MRSA induces acetylation is unclear. Inhibition of either histone acetyltransferases (HATs) (C646) or bromodomain and extra‐terminal domain proteins (BETs) (RVX‐208) attenuates CYP1A1 upregulation. Additionally, MRSA activates the aryl hydrocarbon receptor (Ahr) through an unknown ligand, promoting Ahr translocation into the nucleus to further induce CYP1A1 expression. Blocking Ahr (CH‐223191) attenuates CYP1A1 expression and activity. Inhibiting CYP1A1 activity (Rhapontigenin) attenuates MRSA‐induced disruption of the lung endothelial barrier and associated inflammation. This image was generated using BioRender.com.