Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-β and Nitric Oxide Production

Therapeutic hypothermia protects neurons after injury to the central nervous system (CNS). Microglia express toll-like receptors (TLRs) that play significant roles in the pathogenesis of sterile CNS injury. To elucidate the possible mechanisms involved in the neuroprotective effect of therapeutic hy...

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Main Authors: Tomohiro Matsui, Yukari Motoki, Yusuke Yoshida
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/436263
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author Tomohiro Matsui
Yukari Motoki
Yusuke Yoshida
author_facet Tomohiro Matsui
Yukari Motoki
Yusuke Yoshida
author_sort Tomohiro Matsui
collection DOAJ
description Therapeutic hypothermia protects neurons after injury to the central nervous system (CNS). Microglia express toll-like receptors (TLRs) that play significant roles in the pathogenesis of sterile CNS injury. To elucidate the possible mechanisms involved in the neuroprotective effect of therapeutic hypothermia, we examined the effects of hypothermic culture on TLR3-activated microglial release of interferon (IFN)-β and nitric oxide (NO), which are known to be associated with neuronal cell death. When rat or mouse microglia were cultured under conditions of hypothermia (33°C) and normothermia (37°C) with a TLR3 agonist, polyinosinic-polycytidylic acid, the production of IFN-β and NO in TLR3-activated microglia at 48 h was decreased by hypothermia compared with that by normothermia. In addition, exposure to recombinant IFN-β and sodium nitroprusside, an NO donor, caused death of rat neuronal pheochromocytoma PC12 cells in a concentration-dependent manner after 24 h. Taken together, these results suggest that the attenuation of microglial production of IFN-β and NO by therapeutic hypothermia leads to the inhibition of neuronal cell death.
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spelling doaj-art-38b601caebbe422e804b0ade6ba337a02025-08-20T03:55:11ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/436263436263Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-β and Nitric Oxide ProductionTomohiro Matsui0Yukari Motoki1Yusuke Yoshida2Department of Laboratory Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, JapanDepartment of Laboratory Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, JapanACEL, Inc., SIC1 1201, 5-4-21 Nishihashimoto, Midori-ku, Sagamihara, Kanagawa 252-0131, JapanTherapeutic hypothermia protects neurons after injury to the central nervous system (CNS). Microglia express toll-like receptors (TLRs) that play significant roles in the pathogenesis of sterile CNS injury. To elucidate the possible mechanisms involved in the neuroprotective effect of therapeutic hypothermia, we examined the effects of hypothermic culture on TLR3-activated microglial release of interferon (IFN)-β and nitric oxide (NO), which are known to be associated with neuronal cell death. When rat or mouse microglia were cultured under conditions of hypothermia (33°C) and normothermia (37°C) with a TLR3 agonist, polyinosinic-polycytidylic acid, the production of IFN-β and NO in TLR3-activated microglia at 48 h was decreased by hypothermia compared with that by normothermia. In addition, exposure to recombinant IFN-β and sodium nitroprusside, an NO donor, caused death of rat neuronal pheochromocytoma PC12 cells in a concentration-dependent manner after 24 h. Taken together, these results suggest that the attenuation of microglial production of IFN-β and NO by therapeutic hypothermia leads to the inhibition of neuronal cell death.http://dx.doi.org/10.1155/2013/436263
spellingShingle Tomohiro Matsui
Yukari Motoki
Yusuke Yoshida
Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-β and Nitric Oxide Production
Mediators of Inflammation
title Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-β and Nitric Oxide Production
title_full Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-β and Nitric Oxide Production
title_fullStr Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-β and Nitric Oxide Production
title_full_unstemmed Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-β and Nitric Oxide Production
title_short Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-β and Nitric Oxide Production
title_sort hypothermia reduces toll like receptor 3 activated microglial interferon β and nitric oxide production
url http://dx.doi.org/10.1155/2013/436263
work_keys_str_mv AT tomohiromatsui hypothermiareducestolllikereceptor3activatedmicroglialinterferonbandnitricoxideproduction
AT yukarimotoki hypothermiareducestolllikereceptor3activatedmicroglialinterferonbandnitricoxideproduction
AT yusukeyoshida hypothermiareducestolllikereceptor3activatedmicroglialinterferonbandnitricoxideproduction