Tumor necrosis factor α stimulates endogenous apolipoprotein A-I expression and secretion by human monocytes and macrophages: role of MAP-kinases, NF-κB, and nuclear receptors PPARα and LXRs.

Autor: Shavva VS; Department of Biochemistry, Institute of Experimental Medicine, acad. Pavlov St., 12, Saint Petersburg, Russia, 197376.; Department of Embryology, St. Petersburg State University, Saint Petersburg, Russia., Mogilenko DA; Department of Biochemistry, Institute of Experimental Medicine, acad. Pavlov St., 12, Saint Petersburg, Russia, 197376.; Department of Embryology, St. Petersburg State University, Saint Petersburg, Russia.; Université de Lille, Inserm, Institut Pasteur de Lille, U1011-EGID, 59000, Lille, France., Nekrasova EV; Department of Biochemistry, Institute of Experimental Medicine, acad. Pavlov St., 12, Saint Petersburg, Russia, 197376., Trulioff AS; Department of Immunology, Institute of Experimental Medicine, Saint Petersburg, Russia., Kudriavtsev IV; Department of Immunology, Institute of Experimental Medicine, Saint Petersburg, Russia.; Department of Cytology and Histology, St. Petersburg State University, Saint Petersburg, Russia., Larionova EE; Department of Biochemistry, Institute of Experimental Medicine, acad. Pavlov St., 12, Saint Petersburg, Russia, 197376.; Department of Cytology and Histology, St. Petersburg State University, Saint Petersburg, Russia., Babina AV; Department of Biochemistry, Institute of Experimental Medicine, acad. Pavlov St., 12, Saint Petersburg, Russia, 197376.; Pavlov First St. Petersburg State Medical University, Saint Petersburg, Russia., Dizhe EB; Department of Biochemistry, Institute of Experimental Medicine, acad. Pavlov St., 12, Saint Petersburg, Russia, 197376., Missyul BV; Department of Biochemistry, Institute of Experimental Medicine, acad. Pavlov St., 12, Saint Petersburg, Russia, 197376., Orlov SV; Department of Biochemistry, Institute of Experimental Medicine, acad. Pavlov St., 12, Saint Petersburg, Russia, 197376. serge@iem.sp.ru.; Department of Embryology, St. Petersburg State University, Saint Petersburg, Russia. serge@iem.sp.ru.
Jazyk: angličtina
Zdroj: Molecular and cellular biochemistry [Mol Cell Biochem] 2018 Nov; Vol. 448 (1-2), pp. 211-223. Date of Electronic Publication: 2018 Feb 13.
DOI: 10.1007/s11010-018-3327-7
Abstrakt: 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 α (TNFα) 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 TNFα-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 NFκB, JNK, or p38 blocks an increase of apoA-I gene expression in the macrophages treated with TNFα. Nuclear receptor PPARα 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 PPARα or LXR synthetic ligands as well as knock-down of LXRα, and LXRβ by siRNAs interfered with the TNFα-mediated activation of apoA-I gene in human monocytes and macrophages. At the same time, TNFα differently regulated the levels of PPARα, LXRα, and LXRβ binding to the apoA-I gene promoter in THP-1 cells. Obtained results suggest a novel tissue-specific mechanism of the TNFα-mediated regulation of apoA-I gene in monocytes and macrophages and show that endogenous ApoA-I might be positively regulated in macrophage during inflammation.
Databáze: MEDLINE
Externí odkaz: