title: Effects of estrogen on temporal expressions of IL-1beta and IL-1ra in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation.
abstract: Anti-inflammatory action of estrogen is involved in neuroprotection but the effects of estrogen on IL-1beta and its endogenous antagonist (IL-1 ra) have not been clearly defined in the ischemic brain. This study was performed to evaluate whether estrogen affects the expression of IL-1beta or IL-1ra and the ratio of the two in the ischemic hippocampus. Rat organotypic hippocampal slices were treated with 17beta estradiol (E2, 1 nM) for 7 days, exposed to oxygen-glucose deprivation (OGD) for 30 min, and then reperfused for 72 h. CA1 neuronal death quantified by propidium iodide (PI) staining and expressions of IL-1beta and IL-1ra in slices measured by real-time PCR and Western blotting were examined. PI intensities in CA1 in slices treated with E2 were significantly reduced at 24 h and 72 h post-OGD, and IL-1beta mRNA expressions were reduced at 6 h and 24 h post-OGD. In addition, IL-1ra mRNA was significantly overexpressed and the ratio of IL-1beta to IL-1ra mRNA expression was reduced by E2 especially at 24 h. In terms of protein levels, E2 downregulated IL-1beta but upregulated IL-1ra and thereby decreased the IL-1beta/IL-1 ra ratio at 24h. These findings demonstrate that estrogen-induced protection is associated with a decrease in IL-1beta and an increase in IL-1ra expression in the ischemic hippocampus during early reperfusion periods, which suggests that modulation of IL-1beta/IL-1ra might be a part of anti-inflammatory effects of estrogen.
authors.affiliation: Department of Pharmacology, Ewha Medical Research Institute, School of Medicine, Ewha Womans University, 911-1 Mok6dong Yangcheon-gu, Seoul 158-710, Republic of Korea.
authors.forename: Ji-Seung
authors.initials: JS
authors.lastname: Choi
authors.forename: Soo-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jin A
authors.initials: JA
authors.lastname: Shin
authors.forename: Kyung-Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Park
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004660:Encephalitis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007202:Indicators and Reagents; D053590:Interleukin 1 Receptor Antagonist Protein / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D009924:Organ Culture Techniques; D011419:Propidium; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D004967:Estrogens; D007202:Indicators and Reagents; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D011419:Propidium; D004958:Estradiol