title: Cigarette smoke-induced cerebral cortical interleukin-6 elevation is not mediated through oxidative stress.
abstract: The author group has previously established an in vivo subchronic cigarette smoke (CS) exposure rat model, in which the systemic oxidative burden as well as the modulation of local anti-oxidative enzymes in the lung has been demonstrated. Oxidative stress has been shown to induce pro-inflammatory cytokine release, including interleukin (IL)-6 in the airways. In this study, we aimed to investigate the changes in IL-6 production, as well as the oxidative/anti-oxidative responses in the cerebral cortex using the same in vivo model. IL-6 was determined by RT-PCR and western-blot analysis. Local oxidative and anti-oxidative responses were determined by measuring cerebral cortical malondialdehyde (MDA) and advanced oxidation protein product (AOPP) levels, superoxide dismutase (SOD) and catalase activities, and the reduced to oxidized glutathione (GSH/GSSG) ratio. Nitrite level was measured by fluorescent spectrophotometry. Our results demonstrated a significant increase in both IL-6 mRNA and protein levels. Reductions of SOD activity and manganese (Mn)SOD protein level were observed together with the increased level of superoxide measured by chemiluminescent signal, after 56 days of CS exposure. There were no significant changes in the cerebral cortical levels of MDA, AOPP, catalase activity, and the GSH/GSSG ratio. Nitrite level was significantly reduced, together with the decreased protein level of nNOS in the cerebral cortex, after 56 days of CS exposure. Our results suggest that exposure to CS induces IL-6 expression in the cerebral cortex, which is not mediated by the oxidative/anti-oxidative imbalance.
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Way Kwok-Wai
authors.initials: WK
authors.lastname: Lau
authors.forename: Judith Choi-Wo
authors.initials: JC
authors.lastname: Mak
authors.forename: Ka-Ho
authors.initials: KH
authors.lastname: Chan
authors.forename: Andrew Chi-Kin
authors.initials: AC
authors.lastname: Law
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D013050:Spectrometry, Fluorescence; D013268:Stimulation, Chemical; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014026:Nicotiana / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D015850:Interleukin-6; D012333:RNA, Messenger; D012906:Smoke; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D013482:Superoxide Dismutase