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Cigarette smoke-induced cerebral cortical interleukin-6 elevation is not mediated through oxidative stress.

Lau WK, Mak JC, Chan KH, Law AC - Neurotox Res (2011)

Bottom Line: Our results demonstrated a significant increase in both IL-6 mRNA and protein levels.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.

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.

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Induction of IL-6 in cortex after 56 days of CS exposure. a Expression of IL-6 mRNA, with GNB2L1 serving as an internal control. b Quantitative analysis of luminescent band intensity of IL-6. Results are expressed as IL-6 to GNB2L1 ratio. c Protein levels of IL-6 and gp130, with β-actin serving as an internal control. d, e Quantitative analysis of band intensity by densitometry. Values represent the mean ± SEM. *p < 0.05, when comparing between SA and 56 days of CS exposure groups (n ≥ 4)
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Fig1: Induction of IL-6 in cortex after 56 days of CS exposure. a Expression of IL-6 mRNA, with GNB2L1 serving as an internal control. b Quantitative analysis of luminescent band intensity of IL-6. Results are expressed as IL-6 to GNB2L1 ratio. c Protein levels of IL-6 and gp130, with β-actin serving as an internal control. d, e Quantitative analysis of band intensity by densitometry. Values represent the mean ± SEM. *p < 0.05, when comparing between SA and 56 days of CS exposure groups (n ≥ 4)

Mentions: Our results demonstrated a significant increase of both IL-6 mRNA and protein levels in line with the protein level of gp130 in the rat cerebral cortex after 56 days of CS exposure (Fig. 1). The elevated protein level of gp130 indicated an increased binding of IL-6 to its receptor. Activations of microglia and astrocytes have been associated with the brain inflammation and injury, which can be induced by IL-6 (Balasingam et al. 1994). In our model, we observed no significant changes in the expression of Iba-1 or GFAP in cortex after CS exposure, which is consistent with the earlier literature (Fig. 2, Fuller et al. 2010). These findings suggest that the inflammatory pathway had not yet been activated even when IL-6 levels were elevated in our model.Fig. 1


Cigarette smoke-induced cerebral cortical interleukin-6 elevation is not mediated through oxidative stress.

Lau WK, Mak JC, Chan KH, Law AC - Neurotox Res (2011)

Induction of IL-6 in cortex after 56 days of CS exposure. a Expression of IL-6 mRNA, with GNB2L1 serving as an internal control. b Quantitative analysis of luminescent band intensity of IL-6. Results are expressed as IL-6 to GNB2L1 ratio. c Protein levels of IL-6 and gp130, with β-actin serving as an internal control. d, e Quantitative analysis of band intensity by densitometry. Values represent the mean ± SEM. *p < 0.05, when comparing between SA and 56 days of CS exposure groups (n ≥ 4)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368107&req=5

Fig1: Induction of IL-6 in cortex after 56 days of CS exposure. a Expression of IL-6 mRNA, with GNB2L1 serving as an internal control. b Quantitative analysis of luminescent band intensity of IL-6. Results are expressed as IL-6 to GNB2L1 ratio. c Protein levels of IL-6 and gp130, with β-actin serving as an internal control. d, e Quantitative analysis of band intensity by densitometry. Values represent the mean ± SEM. *p < 0.05, when comparing between SA and 56 days of CS exposure groups (n ≥ 4)
Mentions: Our results demonstrated a significant increase of both IL-6 mRNA and protein levels in line with the protein level of gp130 in the rat cerebral cortex after 56 days of CS exposure (Fig. 1). The elevated protein level of gp130 indicated an increased binding of IL-6 to its receptor. Activations of microglia and astrocytes have been associated with the brain inflammation and injury, which can be induced by IL-6 (Balasingam et al. 1994). In our model, we observed no significant changes in the expression of Iba-1 or GFAP in cortex after CS exposure, which is consistent with the earlier literature (Fig. 2, Fuller et al. 2010). These findings suggest that the inflammatory pathway had not yet been activated even when IL-6 levels were elevated in our model.Fig. 1

Bottom Line: Our results demonstrated a significant increase in both IL-6 mRNA and protein levels.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.

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.

Show MeSH
Related in: MedlinePlus