title: Anti-inflammatory cytokine interleukin-10 increases resistance to brain ischemia through modulation of ischemia-induced intracellular Ca²⁺ response.
abstract: It is suggested that anti-inflammatory cytokine interleukin-10 (IL-10) mediates the delayed protective effects through activation of Jak-Stat3, PI3K-Akt and NF-κB signaling pathways. However, our previous experiments have demonstrated that IL-10 is capable to exert the rapid neuroprotective action through modulation of hypoxia-induced intracellular Ca(2+) ([Ca(2+)]i) response. The first purpose of the present study was to evaluate the neuroprotective effects of IL-10 using three models of the ischemic insults in rats: permanent middle cerebral artery occlusion, ischemia in acute hippocampal slices in vitro and ischemia in cultured hippocampal cells in vitro. The second purpose of the study was to elucidate a role of [Ca(2+)]i changes in the mechanisms underlying IL-10 elicited protection of neurons and astrocytes from ischemia-induced death in cultures of primary hippocampal cells. The data presented here shown that anti-inflammatory cytokine IL-10 is capable to induce a resistance of the brain cells to ischemia-evoked damages in in vivo and in vitro models of the ischemic insults in rats. This protective effect in cultured hippocampal cells is developed rapidly after application of IL-10 and strongly associated with the IL-10 elicited elimination of [Ca(2+)]i response to ischemia. Thus, our results provide the evidence that anti-inflammatory cytokine IL-10, in addition to an activation of the canonical signaling pathways, is capable to exert the rapid neuroprotective effects through transcription-independent modulation of ischemia-induced intracellular Ca(2+) responses in the brain cells.
authors.affiliation: Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Pushchino, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Tukhovskaya
authors.affiliation: Institute of Cell Biophysics of Russian Academy of Sciences, Pushchino, Russia.
authors.forename: Egor A
authors.initials: EA
authors.lastname: Turovsky
authors.affiliation: Institute of Cell Biophysics of Russian Academy of Sciences, Pushchino, Russia.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Turovskaya
authors.affiliation: Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, Pushchino, Russia.
authors.forename: Sergei G
authors.initials: SG
authors.lastname: Levin
authors.affiliation: Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Pushchino, Russia.
authors.forename: Arkady N
authors.initials: AN
authors.lastname: Murashev
authors.affiliation: Institute of Cell Biophysics of Russian Academy of Sciences, Pushchino, Russia.
authors.forename: Valery P
authors.initials: VP
authors.lastname: Zinchenko
authors.affiliation: Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, Pushchino, Russia. Electronic address: Oleg-godukhin@rambler.ru.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Godukhin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D016753:Interleukin-10; D002118:Calcium
keywords: Brain ischemia; Ca(2+); Cultured hippocampal cells; Hippocampal slices; Interleukine-10; Middle cerebral artery occlusion