학술논문
Tumor necrosis factor [alpha] stimulates endogenous apolipoprotein A-I expression and secretion by human monocytes and macrophages: role of MAP-kinases, NF-[kappa]B, and nuclear receptors PPAR[alpha] and LXRs
Article
Article
Document Type
Academic Journal
Author
Source
Molecular and Cellular Biochemistry. November 2018, Vol. 448 Issue 1-2, p211, 13 p.
Subject
Language
English
ISSN
0300-8177
Abstract
Author(s): Vladimir S. Shavva [sup.1] [sup.2] , Denis A. Mogilenko [sup.1] [sup.2] [sup.6] , Ekaterina V. Nekrasova [sup.1] , Andrey S. Trulioff [sup.3] , Igor V. Kudriavtsev [sup.3] [sup.4] , [...]
Apolipoprotein A-I (ApoA-I) is the main structural and functional protein component of high-density lipoprotein. ApoA-I has been shown to regulate lipid metabolism and inflammation in macrophages. Recently, we found the moderate expression of endogenous apoA-I in human monocytes and macrophages and showed that pro-inflammatory cytokine tumor necrosis factor [alpha] (TNF[alpha]) increases apoA-I mRNA and stimulates ApoA-I protein secretion by human monocytes and macrophages. Here, we present data about molecular mechanisms responsible for the TNF[alpha]-mediated activation of apoA-I gene in human monocytes and macrophages. This activation depends on JNK and MEK1/2 signaling pathways in human monocytes, whereas inhibition of NF[kappa]B, JNK, or p38 blocks an increase of apoA-I gene expression in the macrophages treated with TNF[alpha]. Nuclear receptor PPAR[alpha] is a ligand-dependent regulator of apoA-I gene, whereas LXRs stimulate apoA-I mRNA transcription and ApoA-I protein synthesis and secretion by macrophages. Treatment of human macrophages with PPAR[alpha] or LXR synthetic ligands as well as knock-down of LXR[alpha], and LXR[beta] by siRNAs interfered with the TNF[alpha]-mediated activation of apoA-I gene in human monocytes and macrophages. At the same time, TNF[alpha] differently regulated the levels of PPAR[alpha], LXR[alpha], and LXR[beta] binding to the apoA-I gene promoter in THP-1 cells. Obtained results suggest a novel tissue-specific mechanism of the TNF[alpha]-mediated regulation of apoA-I gene in monocytes and macrophages and show that endogenous ApoA-I might be positively regulated in macrophage during inflammation.
Apolipoprotein A-I (ApoA-I) is the main structural and functional protein component of high-density lipoprotein. ApoA-I has been shown to regulate lipid metabolism and inflammation in macrophages. Recently, we found the moderate expression of endogenous apoA-I in human monocytes and macrophages and showed that pro-inflammatory cytokine tumor necrosis factor [alpha] (TNF[alpha]) increases apoA-I mRNA and stimulates ApoA-I protein secretion by human monocytes and macrophages. Here, we present data about molecular mechanisms responsible for the TNF[alpha]-mediated activation of apoA-I gene in human monocytes and macrophages. This activation depends on JNK and MEK1/2 signaling pathways in human monocytes, whereas inhibition of NF[kappa]B, JNK, or p38 blocks an increase of apoA-I gene expression in the macrophages treated with TNF[alpha]. Nuclear receptor PPAR[alpha] is a ligand-dependent regulator of apoA-I gene, whereas LXRs stimulate apoA-I mRNA transcription and ApoA-I protein synthesis and secretion by macrophages. Treatment of human macrophages with PPAR[alpha] or LXR synthetic ligands as well as knock-down of LXR[alpha], and LXR[beta] by siRNAs interfered with the TNF[alpha]-mediated activation of apoA-I gene in human monocytes and macrophages. At the same time, TNF[alpha] differently regulated the levels of PPAR[alpha], LXR[alpha], and LXR[beta] binding to the apoA-I gene promoter in THP-1 cells. Obtained results suggest a novel tissue-specific mechanism of the TNF[alpha]-mediated regulation of apoA-I gene in monocytes and macrophages and show that endogenous ApoA-I might be positively regulated in macrophage during inflammation.