The apoA-I induced transcriptome and dependence on MyD88

Apolipoprotein A-I is well known to play a role in cholesterol efflux, but our studies suggest that apoA-I may also induce proinflammatory signaling. The molecular mechanisms behind apoA-I-mediated proinflammatory signaling have not yet been explored, nor has the link between this signaling and cholesterol efflux. We hypothesize that apoA-I is a novel TLR agonist, signaling through the MyD88 proinflammatory signaling adaptor to induce cytokines. Microarray analysis confirmed that a suite of pro-inflammatory genes are induced by apoA-I with varying dependence upon MyD88, and that MyD88 regulates >6% of the apoA-I-induced transcriptome. Three replicate experiments were analyzed. Each experiment consisted of a control sample and an apoA-I treated sample of RNA extracted from peritoneal macrophages isolated from both MyD88 +/+ and MyD88-/- mice, totaling four samples per experiment; 12 samples together.