Figure 3.

Mechanisms of inflammation caused by abnormal cholesterol. Cholesterol could promote inflammation by activating the TLR signaling pathway to facilitate the release of pro-inflammatory cytokines, and the TLR signaling could be amplified by excess cholesterol in macrophages to exacerbate the inflammatory response. The NLRP3 can be activated by cholesterol and releases IL-1 via the caspase-1-mediated pro-inflammatory IL-1 signaling pathway. IL-1 released after NLRP3 activation shares the intracellular signaling domain with TLRs, inducing MyD88 to produce additional inflammatory mediators that aggravate the inflammatory response. Cholesterol induces the release of NETs, which in turn stimulate macrophages to produce cytokines that activate TH17 cells. The formation of NETs is also associated with the activation of NLRP3. These mechanisms of action do not exist independently but instead are closely related to each other, thereby exacerbating the cholesterol-induced inflammatory response. Abbreviations: TLR, toll-like receptor; LPS, lipopolysaccharide; TIR, Toll/IL-1 receptor; IL-1β, interleukin-1β; MyD88, major reactive protein 88; NETs, neutrophil extracellular traps; PM, plasma membrane; ER, endoplasmic reticulum; TH17, T-helper cell 17; HDL, high-density lipoprotein.