title: Effects of cobalt chloride on nitric oxide and cytokines/chemokines production in microglia.
abstract: The involvement of microglial activation in metal neurotoxicity is becoming increasingly recognized. Some metal ions, such as zinc (II) and manganese (II), have been recently reported as microglial activators to induce the release of inflammatory mediators including cytokines, chemokines and nitric oxide (NO) which are involved in the pathogenesis of neurological diseases. Cobalt is essential for human life. However, excessive cobalt is cytotoxic and neurotoxic. In the present study, we determined cobalt-induced production of NO and cytokines/chemokines in N9 cells, a murine microglial cell line. High levels of cobalt significantly up-regulated iNOS mRNA and protein expression, which resulted in the release of NO. Cobalt induced the production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in a concentration- and time-dependent manner in both N9 cells and primary mouse microglia and increased lipopolysaccharides (LPS)-induced cytokine production. Further study showed that cobalt induced cytokine production by a mechanism involving both nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. The involvement of reactive oxygen species (ROS) in microglial activation was also confirmed. These findings suggested that cobalt neurotoxicity should be attributed not only directly to neuronal damage but also indirectly to microglial activation which might potentiate neuronal injury via elevation of proinflammatory mediator levels.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Yan Hua
authors.initials: YH
authors.lastname: Mou
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Yang
authors.forename: Nan
authors.initials: N
authors.lastname: Cui
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Hou
authors.forename: Shuang
authors.initials: S
authors.lastname: Song
authors.forename: Chun Fu
authors.initials: CF
authors.lastname: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D003035:Cobalt / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003035:Cobalt; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C018021:cobaltous chloride