Yunnan Lu1, Guodong Xiao, Weifeng Luo. 1. Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Abstract
OBJECTIVE: Minocycline, a tetracycline antibiotic, has shown anti-inflammatory effects in cerebral ischemia and neurodegenerative disease; however, the molecular mechanisms underlying this effect have not been clearly identified. Since NLRP3 inflammasome activation controls the maturation and release of proinflammatory cytokines, especially interleukin-1β (IL-1β) and IL-18 in ischemia stroke, we suppose that minocycline may be involved in the regulation of NLRP3 inflammasome activation. METHODS: We investigated the effects of minocycline on NLRP3 inflammasome activation using the transient middle cerebral artery occlusion (tMCAO) mouse model and an in vitro oxygen-glucose deprivation/reoxygenation injury model in BV2 microglial cells. RESULTS: We found that minocycline administrated 1 h after reperfusion can improve neurological disorder, reduce infarct volume, and alleviate cerebral edema. Meanwhile, we showed that minocycline prevented the activation of microglias and attenuated NLRP3 inflammasome signaling after tMCAO injury. Furthermore, we found that the pretreatment of minocycline significantly inhibited signal 1 and signal 2 of NLRP3 inflammasome activation in BV2 cells. CONCLUSION: We demonstrated that minocycline can ameliorate ischemia-induced brain damage via inhibiting NLRP3 inflammasome activation.
OBJECTIVE:Minocycline, a tetracycline antibiotic, has shown anti-inflammatory effects in cerebral ischemia and neurodegenerative disease; however, the molecular mechanisms underlying this effect have not been clearly identified. Since NLRP3 inflammasome activation controls the maturation and release of proinflammatory cytokines, especially interleukin-1β (IL-1β) and IL-18 in ischemia stroke, we suppose that minocycline may be involved in the regulation of NLRP3 inflammasome activation. METHODS: We investigated the effects of minocycline on NLRP3 inflammasome activation using the transient middle cerebral artery occlusion (tMCAO) mouse model and an in vitro oxygen-glucose deprivation/reoxygenation injury model in BV2 microglial cells. RESULTS: We found that minocycline administrated 1 h after reperfusion can improve neurological disorder, reduce infarct volume, and alleviate cerebral edema. Meanwhile, we showed that minocycline prevented the activation of microglias and attenuated NLRP3 inflammasome signaling after tMCAO injury. Furthermore, we found that the pretreatment of minocycline significantly inhibited signal 1 and signal 2 of NLRP3 inflammasome activation in BV2 cells. CONCLUSION: We demonstrated that minocycline can ameliorate ischemia-induced brain damage via inhibiting NLRP3 inflammasome activation.
Authors: Konrad Peukert; Mario Fox; Susanne Schulz; Caroline Feuerborn; Stilla Frede; Christian Putensen; Hermann Wrigge; Beate Mareike Kümmerer; Sascha David; Benjamin Seeliger; Tobias Welte; Eicke Latz; Dennis Klinman; Christoph Wilhelm; Folkert Steinhagen; Christian Bode Journal: Am J Respir Crit Care Med Date: 2021-07-01 Impact factor: 21.405