Inflammatory stress signaling via NF-kB alters accessible cholesterol to upregulate SREBP2 transcriptional activity in endothelial cells

• DOI: 10.7554/elife.79529
• Publication Date: 2022-08-12T10:16:14Z
• Authors: Joseph Wayne M Fo...; Rong Zhang; Bo Tao; Nabil E Boutagy; William C Sessa
• Keywords: Homeostasis; Oxysterol

There is a growing appreciation that tight relationship exists between cholesterol homeostasis and immunity in leukocytes; however, this has not been deeply explored the vascular endothelium. Endothelial cells (ECs) rapidly respond to extrinsic signals, such as tissue damage or microbial infection, by upregulating factors activate recruit circulating leukocytes site of injury aberrant activation ECs leads inflammatory based diseases, multiple sclerosis atherosclerosis. Here, we studied role key transcription regulator homeostasis, SREBP2, EC responses stress. Treatment primary human with pro-inflammatory cytokines upregulated SREBP2 cleavage biosynthetic gene expression within late phase acute response. Furthermore, was dependent on NF-κB DNA binding canonical SCAP-SREBP2 processing. Mechanistically, SREBP mediated reduction accessible cholesterol, leading heightened sterol sensing downstream cleavage. Detailed analysis inducible genes may impact resulted identification novel RELA -inducible target, STARD10 , mediates ECs. Thus, study provides an in-depth characterization response EC.