title: Norepinephrine induces the expression of interleukin-6 via β-adrenoreceptor-NAD(P)H oxidase system -NF-κB dependent signal pathway in U937 macrophages.
abstract: Atherosclerosis is an inflammatory disease in the vessel wall. IL-6 is a mediator of inflammation and a major alarm hormone signaling tissue damage and infection to the body's host defense system, in particular to the liver, where it induces the synthesis of acute phase plasma proteins. Although Norepinephrine (NE) can stimulate the vascular cells to produce IL-6, it is unknown whether NE induces IL-6 expression in macrophages. The present study was to observe effect of NE on IL-6 production and the related signal pathway in U937 macrophages so as to provide more evidence for the proinflammatory action of NE. The results showed that NE significantly increased mRNA and protein expression of IL-6 in U937 macrophages in time- and concentration-dependent manners. β-adrenoreceptor inhibitor propranolol blocked NE-induced IL-6 expression in mRNA and protein levels in U937 macrophages. Propranolol and DPI [NAD(P)H oxidase inhibitor] decreased NE-stimulated reactive oxygen species (ROS) generation, and antioxidant NAC completely abolished NE-induced IL-6 expression in U937 macrophages. The further study indicated that NAD(P)H oxidase inhibitor DPI and NF-κB inhibitor PDTC reduced NE-induced mRNA and protein expression of IL-6 in U937 macrophages. These demonstrate that NE is capable of inducing IL-6 generation in macrophages via β-ADR-ROS-NF-κB signal pathway, which contributes to better understanding of the proinflammatory and proatherosclerotic actions of NE.
authors.affiliation: Department of Pharmacy, Lianyungang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Lianyungang, Jiang Su Province 222000, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Acupuncture and Moxibustion, Lianyungang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Lianyungang, Jiang Su Province 222000, People's Republic of China. Electronic address: liminglm1985@163.com.
authors.forename: Wenping
authors.initials: W
authors.lastname: Yao
authors.affiliation: Board of Health, Yicheng District, Zaozhuang City, Shandong Province 277300, People's Republic of China.
authors.forename: Shenqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Operating Room, Affiliated Hospital of Jining Medical College, Jining, Shandong Province 272029, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xi
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D020298:U937 Cells
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D011943:Receptors, Adrenergic, beta; D019255:NADPH Oxidases; D009638:Norepinephrine
keywords: Atherosclerosis; Inflammation; Interleukin-6; Macrophages; Norepinephrine