ER Stress Activates the NLRP3 Inflammasome: A Novel Mechanism of Atherosclerosis

Figure 4

SREBP pathway mediated NLRP3 inflammasome activation. ER stress activates the SREBP pathway to maintain lipid homeostasis. NLRP3 associates with SCAP-SREBP-2 to form a ternary complex which translocates from the ER to the Golgi, where the complex is cleaved by S1P and S2P. The cleaved NLRP3 can be used for inflammasome assembly. SREBP-2, on the other hand, stimulates NOX2 and NLRP3 expression transcriptionally which in turn affects the inflammasome activation process. As an important ER stress factor, BiP overexpression affects ER lipid metabolism via significantly inhibiting SREBP-2 and downstream target gene expression. SREBP: sterol regulatory element-binding protein; NLRP3: nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3; ER: endoplasmic reticulum; SCAP: SREBP cleavage-activating protein; S1P: site 1 protease; S2P: site 2 protease; NOX2: NADPH oxidase 2; BiP: binding protein.