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Interleukin-32 promotes lipid accumulation through inhibition of cholesterol efflux.


ABSTRACT: Interleukin-32 (IL-32) is a pro-inflammatory cytokine and its effects in various inflammatory diseases have been investigated. However, the role of IL-32 on atherosclerosis, an inflammatory disease, remains unknown. The present study examined the use of IL-32?, the most abundant transcript of IL-32, in the treatment of oxidized low-density lipoprotein (ox-LDL)-stimulated THP-1 macrophages for 24 h, which simulates a foam cell formation model. The effect of IL-32? (20, 50 and 100 ng/ml) on lipid deposition in the macrophages was analyzed using Oil Red O staining, while the cholesterol efflux on apolipoprotein A-I was also measured. The mRNA and protein expression levels of peroxisome proliferator-activated receptor ? (PPAR?), liver X receptor ? (LXR?), ATP-binding cassette transporter A1 (ABCA1) and ABCG1 were quantified by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The results indicated that IL-32? exposure enhanced the lipid deposition and attenuated the cholesterol efflux from ox-LDL-stimulated THP-1 macrophages in a dose-dependent manner. Furthermore, the expression levels of ABCA1, LXR? and PPAR? were dose-dependently decreased by IL-32? at the mRNA and protein levels. Addition of the PPAR? agonist 15d-PGJ2 or overexpression of PPAR? in THP-1 macrophages abrogated the IL-32?-mediated inhibition of cholesterol efflux and reversed the IL-32?-mediated downregulation of ABCA1 and LXR?. In conclusion, IL-32? enhances lipid accumulation and inhibits cholesterol efflux from ox-LDL-exposed THP-1 macrophages by regulating the PPAR?-LXR?-ABCA1 pathway.

SUBMITTER: Xu Z 

PROVIDER: S-EPMC5526182 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Interleukin-32 promotes lipid accumulation through inhibition of cholesterol efflux.

Xu Zonglei Z   Dong Aizhi A   Feng Zerui Z   Li Jing J  

Experimental and therapeutic medicine 20170613 2


Interleukin-32 (IL-32) is a pro-inflammatory cytokine and its effects in various inflammatory diseases have been investigated. However, the role of IL-32 on atherosclerosis, an inflammatory disease, remains unknown. The present study examined the use of IL-32α, the most abundant transcript of IL-32, in the treatment of oxidized low-density lipoprotein (ox-LDL)-stimulated THP-1 macrophages for 24 h, which simulates a foam cell formation model. The effect of IL-32α (20, 50 and 100 ng/ml) on lipid  ...[more]

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