title: Ox-LDL Upregulates IL-6 Expression by Enhancing NF-κB in an IGF2-Dependent Manner in THP-1 Macrophages.
abstract: Interleukin 6 (IL-6) is a pro-inflammatory cytokine that is well established as a vital factor in determining the risk of coronary heart disease and pathogenesis of atherosclerosis. Moreover, accumulating evidences have shown that oxidized low-density lipoprotein (ox-LDL) can promote IL-6 expression in macrophages. Nevertheless, the underlying mechanism of how ox-LDL upregulates IL-6 expression remains largely unexplained. We found that the expression of insulin-like growth factor 2 (IGF2), nuclear factor kappa B (NF-κB), and IL-6 was upregulated at both the messenger RNA (mRNA) and protein levels in a dose-dependent manner when treated with 0, 25, 50, or 100 μg/mL of ox-LDL for 48 h in THP-1 macrophages. Moreover, overexpression of IGF2 significantly upregulated NF-κB and IL-6 expressions in THP-1 macrophages. However, the upregulation of NF-κB and IL-6 expressions induced by ox-LDL were significantly abolished by IGF2 small interfering RNA (siRNA) in THP-1 macrophages. Further studies indicated the upregulation of IL-6 induced by ox-LDL could be abolished when treated with NF-κB siRNA in THP-1 macrophages. Ox-LDL might upregulate IL-6 in the cell and its secretion via enhancing NF-κB in an IGF2-dependent manner in THP-1 macrophages.
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Yan-Chao
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Hu
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Sha
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Ji-Juan
authors.initials: JJ
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Li
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Zhao
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Qiu
authors.affiliation: Department of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Lu
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Huang
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhao
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China. nfyyzl@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China. nfyywangqian@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D015854:Up-Regulation
chemical_list: C035170:IGF2 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D007335:Insulin-Like Growth Factor II
keywords: IGF2; IL-6; NF-κB; Ox-LDL; THP-1 macrophages