Kv1.1 expression in microglia regulates production and release of proinflammatory cytokines, endothelins and nitric oxide

• Published in: Neuroscience 2009-02, Vol.158 (4), p.1500-1508
• Main Authors: Wu, C.-Y, Kaur, C, Sivakumar, V, Lu, J, Ling, E.-A
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Animals, Newborn; Antibodies - pharmacology; Biological and medical sciences; Brain - cytology; Brain - growth & development; Brain - metabolism; Cell Line, Transformed; Colorimetry - methods; Cytokines - metabolism; endothelins; Endothelins - metabolism; Enzyme-Linked Immunosorbent Assay - methods; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; hypoxia; Hypoxia - metabolism; Hypoxia - pathology; Kv1.1; Kv1.1 Potassium Channel - genetics; Kv1.1 Potassium Channel - immunology; Kv1.1 Potassium Channel - metabolism; Lipopolysaccharides - pharmacology; Mice; microglia; Microglia - drug effects; Microglia - metabolism; Neurology; nitric oxide; Nitric Oxide - genetics; Nitric Oxide - metabolism; proinflammatory cytokines; Rats; Rats, Wistar; RNA, Messenger - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.11.043

Abstract Potassium channels play an important role in microglial activation but their involvement in main functions of microglia including secretion of proinflammatory cytokines has remained uncertain. This study has revealed the specific expression of Kv1.1 in microglia both in vivo and in vitro . Kv1.1 immunoreactivity was localized in the amoeboid microglia in the rat brain between postnatal (P) day 1 (P1) and day 10 (P10); it was, however, progressively reduced with age and was hardly detected at P14 and P21 in ramified microglia, a derivative cell of amoeboid microglia. Following hypoxic exposure, Kv1.1 expression in amoeboid microglia was enhanced or induced in ramified microglia in more mature brain at P21 when compared with their matching controls. RT-PCR and Western blot analysis confirmed Kv1.1 mRNA and protein expression in murine BV-2 cells which was up-regulated by hypoxia or lipopolysaccharide (LPS) treatment; it was reduced significantly by dexamethasone. Neutralization with Kv1.1 antibody suppressed the expression and release of tumor necrosis factor-α, interleukin-1β, endothelins and nitric oxide (NO) in LPS-activated BV-2 cells. It is concluded that Kv1.1, constitutively expressed by microglia, is elicited by hypoxia and LPS and this may be linked to production of proinflammatory cytokines, endothelins and NO.