Curcumin affects ox‑LDL‑induced IL‑6, TNF‑α, MCP‑1 secretion and cholesterol efflux in THP‑1 cells by suppressing the TLR4/NF‑κB/miR33a signaling pathway

Abstract

The aim of the present study was to study the molecular mechanism of how curcumin decreases the formation of ox-LDL induced human monocyte macrophage foam cells, promotes the efflux of cholesterol and reduces the secretion of inflammatory cytokines. In vitro cultured THP-1 cells were induced to become macrophages using phorbol-12-myristate-13-acetate. The cells were then pre-treated with curcumin before inducing the foam cell model by addition of oxidized low-density lipoprotein (ox-LDL). Western blot assays were used to detect expression levels of toll-like receptor (TLR)4, nuclear factor κB (NF-κB), NF-κB inhibitor α (IκBα), phosphorylated-IκBα and ATP binding cassette transporter (ABC)A1. Reverse transcription-quantitative PCR was employed to examine mRNA levels of TLR4, microRNA (miR)33a and ABCA1. ELISAs were used to detect inflammatory factors, including tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1 and interleukin (IL)-6. ox-LDL successfully induced the foam cell model, promoted phosphorylation of IκBα, promoted nuclear translocation of NF-κB, promoted the expression of TLR4 and miR33a, and promoted the secretion of TNF-α, MCP-1 and Il-6. Additionally, ox-LDL reduced the expression of ABCA1 and cholesterol efflux. However, pretreatment with curcumin increased the expression of ABCA1 and cholesterol efflux and suppressed secretion of TNF-α, MCP-1 and Il-6. TLR4 antibodies, the NF-κB blocker, PDTC, and the miR33a inhibitor also reduced the abnormal transformations induced by ox-LDL. Curcumin promoted cholesterol efflux by suppressing the TLR4/NF-κB/miR33a signaling pathway, and reduced the formation of foam cells and the secretion of inflammatory factors.

Artesunate attenuates foam cell formation by enhancing cholesterol efflux

“…Absence or damage of ABCA1, ABCG1, or SR-BI function can promote the accumulation of foam cells, leading to atherosclerotic lesions and excessive inflammation (30)(31)(32). As previously demonstrated, curcumin can mediate the increase in cholesterol efflux in macrophages by heme oxygenase-1-mediated ABCA1 and SR-BI, while perilla extract and α-asarone can also increase ox-LDL-induced cholesterol efflux in macrophages (25). In the present study, we found that ART increased the ox-LDL-induced expression of ABCA1 and ABCG1 in THP-1-derived macrophages without effect on the SR-BI.…”

“…When cholesterol efflux and esterification increase, or cholesterol outflow decreases, macrophages eventually become lipid-rich foam cells. Recent studies have shown that some traditional Chinese medicines and/or their extracts, such as curcumin, purple perilla, tanshinone IIA, and astragalin exhibit an anti-atherosclerotic effect, which is closely related to an increase in cholesterol efflux (25)(26)(27).…”

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

“… 386 PMA is also the standard substance used to differentiate human monocytic leukemia cells into THP-1 macrophages – a standard host system for ABCA transporter evaluation. 231 , 245 , 249 , 256 , 268 , 272 , 275 , 292 , 308 , 310 , 312 - 316 , 321 , 328 , 335 , 338 , 339 , 341 , 342 , 360 , 363 , 364 , 366 , 377 , 384 , 388 - 397 …”

“…Regarding the AMPK pathway ( Figure 3 ), the natural compound curcumin induced ABCA1 / Abca1 mRNA 338 , 388 and ABCA1 protein levels 388 , 394 as well as cholesterol efflux 338 , 388 , 394 in THP-1 338 , 388 , 394 and RAW264.7 394 macrophages, which was also mediated through LXR-α activation. 338 However, these LXR-α activating effects were much more pronounced in combination with the gold standard TO901317.…”

“…In terms of ABCA1, most studies have been conducted with human THP1, 231 , 245 , 249 , 256 , 268 , 272 , 275 , 292 , 308 , 310 , 312 - 316 , 321 , 328 , 335 , 338 , 339 , 341 , 342 , 360 , 363 , 364 , 366 , 377 , 384 , 388 - 397 murine J774.A1, 252 , 254 , 255 , 259 , 265 , 271 , 278 , 289 - 292 , 384 , 392 , 393 or murine RAW264.7 macrophages. 230 , 249 , 312 , 313 , 321 , 336 , 339 , 342 , 352 , 360 , 365 , 367 , 369 , 375 , 376 , 381 , 385 , 399 , 402 , 404 , 406 , 408 , 410 , 416 - ...…”