Effect Of IL-37on THP-1Differentiated Foam Cells Formation

Objective: IL-37，recently identified as a natural suppressor of innate inflammatory andimmune response，exerts a suppressive activity on various chronic inflammatory diseasesbut the underlying mechanism remains unclear. Here, we investigated whether and howIL-37affects macrophages foam-cell formation, and thereby investigated the mechanism ofIL-37in the development of atherosclerosis.Method: THP-1cells were differentiated into macrophages using160nM PMA for24h.And then with ox LDL or IL37combine with ox LDL in FBS-free growth medium for24hours to transform macrophages into foam cells. THP-1cells differentiated macrophageswere stimulated with ox LDL24h，then with10ng/ml IL-37for another24hours. Oil red Ostaining and cellular lipid measurement were used to identify macrophage foam cellformation. Real-time PCR and western blot were carried out to explore the mechanism ofIL-37-mediated suppression on THP-1-macrophages derived foam cell formation.Result: Oil Red O staining identified foam cell formation was signifcantly reduced in cellstreated with IL-37and ox LDL (Fig.1B).The similar effect of IL37was obtained whenextracted oil red O and measured by a spectrophotometer. Compared with ox LDL alone,IL-37and ox LDL significantly reduced the lipids accumulation in macrophage foam cellsin a concentration-dependent manner. Total cellular cholesterol was significantly reduced inIL-37and ox LDL cultures relative to ox LDL alone (TC:150.4±7.36vs.303.1±8.9ng/mg,p<0.01) Moreover, real-time PCR and western blot analysis showed that the expression ofboth CD36and SRA of macrophage foam cells treated by ox LDL together with IL-37was significantly down-regulated, while ABCA-1up-regulated significantly.Conclusion: Results collectively suggest that IL-37may inhibit THP-1differentiatedmacrophage foam-cell formation, which is largely caused by a down-regulated expressionof scavenger receptor SRA and CD36and up-regulated expression of ABCA-1.