Interleukin-32 upregulates the expression of ABCA1 and ABCG1 resulting in reduced intracellular lipid concentrations in primary human hepatocytes.
Atherosclerosis
; 271: 193-202, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29524862
ABSTRACT
BACKGROUND AND AIMS:
The role of interleukin (IL-)32 in inflammatory conditions is well-established, however, the mechanism behind its role in atherosclerosis remains unexplained. Our group reported a promoter single nucleotide polymorphism in IL-32 associated with higher high-density lipoprotein (HDL) concentrations. We hypothesize that endogenous IL-32 in liver cells, a human monocytic cell line and carotid plaque tissue, can affect atherosclerosis by regulating (HDL) cholesterol homeostasis via expression of cholesterol transporters/mediators.METHODS:
Human primary liver cells were stimulated with recombinant human (rh)TNFα and poly IC to study the expression of IL-32 and mediators in cholesterol pathways. Additionally, IL-32 was overexpressed in HepG2 cells and overexpressed and silenced in THP-1â¯cells to study the direct effect of IL-32 on cholesterol transporters expression and function.RESULTS:
Stimulation of human primary liver cells resulted in induction of IL-32α, IL-32ß and IL-32γ mRNA expression (pâ¯<â¯0.01). A strong correlation between the expression of IL-32γ and ABCA1, ABCG1, LXRα and apoA1 was observed (pâ¯<â¯0.01), and intracellular lipid concentrations were reduced in the presence of endogenous IL-32 (pâ¯<â¯0.05). Finally, IL32γ and ABCA1 mRNA expression was upregulated in carotid plaque tissue and when IL-32 was silenced in THP-1â¯cells, mRNA expression of ABCA1 was strongly reduced.CONCLUSIONS:
Regulation of IL-32 in human primary liver cells, HepG2 and THP-1â¯cells strongly influences the mRNA expression of ABCA1, ABCG1, LXRα and apoA1 and affects intracellular lipid concentrations in the presence of endogenous IL-32. These data, for the first time, show an important role for IL32 in cholesterol homeostasis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucinas
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Hepatócitos
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Transportador 1 de Cassete de Ligação de ATP
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Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP
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HDL-Colesterol
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article