title: Visfatin contributes to the differentiation of monocytes into macrophages through the differential regulation of inflammatory cytokines in THP-1 cells.
abstract: Visfatin is a novel multifunctional adipocytokine with inflammatory properties. Although a link between visfatin and atherosclerosis has recently been suggested, its actions in the development of atherosclerosis remain unknown. Therefore, we investigated a potential role and underlying mechanism(s) of visfatin in monocytes/macrophages differentiation, a critical early step in atherogenesis, using phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cell models. The co-incubation of PMA with visfatin-induced CD36 expression with a concomitant increase in the phagocytosis of latex beads compared with PMA alone treatment. Moreover, visfatin markedly increased interleukin (IL)-1β secretion by enhancing IL-1β mRNA stability in a short-term incubation. Visfatin also significantly elevated the secretion of IL-6 as well as IL-1β in a longer incubation period, which was partially suppressed by nuclear factor-κB (NF-κB) inhibitor, BAY11-7082, and c-Jun-N-terminal kinase (JNK) inhibitor, SP600125. Furthermore, silencing IL-1β successfully blocked IL-6 secretion, CD36 expression, and NF-κB activation in response to visfatin. Collectively, these results suggest that visfatin enhances the IL-1β-dependent induction of IL-6 and CD36 via distinct signaling pathways mediated by JNK and NF-κB, respectively, and consequently, leading to the acceleration of monocytes/macrophages differentiation.
authors.affiliation: Division of Cardiovascular and Rare Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Republic of Korea; JE-UK Laboratory of Molecular Cancer Therapeutics, Yonsei Cancer Research Institute, College of Medicine, Yonsei University, Seoul, Republic of Korea.
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Yun
authors.affiliation: Division of Cardiovascular and Rare Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Republic of Korea.
authors.forename: Jeong Mi
authors.initials: JM
authors.lastname: Seo
authors.affiliation: Division of Cardiovascular and Rare Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Republic of Korea. Electronic address: mdhypark@gmail.com.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Park
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D018955:CD36 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000873:Anthracenes; D018955:CD36 Antigens; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D009570:Nitriles; D010703:Phorbol Esters; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D013450:Sulfones; C432165:pyrazolanthrone; C119222:phorbol-12-myristate; D054409:Nicotinamide Phosphoribosyltransferase; D048031:JNK Mitogen-Activated Protein Kinases
keywords: CD36; IL-1β; IL-6; Monocytes/macrophages differentiation; NF-κB; Visfatin