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

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). (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, CEP-37440 which is not mediated by the oxidative/anti-oxidative imbalance. Keywords:Neuroinflammation, Nitric oxide, Reactive oxygen species, Smoking Interleukin (IL)-6 is a cytokine that mediates immune responses and inflammation processes. In the 1980s, IL-6 was first discovered to be produced by lymphocytes that mediated differentiation of B-cells (Hirano et al.1986; Van Damme et al.1987). Molecular pathway of IL-6 is initiated by the binding of IL-6 to its cell surface receptor, which triggers the recruitment of the signal transducer subunit gp130 (Heinrich et al.2003), and induces the second messenger cascade. The inflammatory roles of IL-6 are contradictory. IL-6 has been reported to be involved in both pro-, and anti-inflammatory processes CEP-37440 (Spooren et al.2011). As an inflammatory cytokine, IL-6 plays a particularly important role in neuronal defensive mechanisms. It has been reported that the overexpression of IL-6 promotes astrogliosis and microgliosis in different in vivo models (Fattori et al.1995; Tilgner et al.2001). On the other hand, IL-6 is suggested to have an anti-inflammatory role, contributing toward the maintenance of the bloodbrain barrier (BBB) integrity under neuroinflammatory conditions (Milner and Campbell2006). Other than being an inflammatory cytokine, IL-6 is also considered as a neurotrophic factor. It has been shown to enhance neuronal differentiation in different cell types (Cao et al.2006; Sterneck et al.1996; Zhang et al.2007) and promote neurogenesis (Islam et al.2009). The exact role of IL-6 in neurological disorders is yet to be fully understood; however, elevated IL-6 level has been associated with many neurological diseases, including multiple sclerosis (Maimone et al.1991), dementia (Zuliani et al.2007), Parkinsons disease (Nagatsu et al.2000), autism, and schizophrenia (Patterson2009). An in vivo study demonstrated that maternal immune activationa popular hypothesis regarding the pathogenesis of neurodevelopmental disordersfailed to induce the behavior changes associated with autism and schizophrenia in IL-6/mice offspring model compared to that of the wild-type strain (Smith et al.2007), indicating the role of IL-6. Cigarette smoking is not only a major risk factor for airway diseases, but also for neurodegenerative disorders, including Alzheimers disease (AD, Ronnemaa et al.2011; Barnes and Yaffe2011). Cigarette smoke (CS) induces oxidative damage in different ways. Free radicals generated by CS induce lipid peroxidation, which can be measured by its byproducts, 8-isoprostane and malondialdehyde (MDA, Armstrong and Browne1994). On the other hand, oxidant-mediated protein damage can be determined by the level of advanced oxidation protein products (AOPP, Witko-Sarsat et al.1996). The oxidative/anti-oxidative imbalance that is triggered by long-term exposure to the abundant reactive oxygen species (ROS) in CS is known to induce Rabbit Polyclonal to KLF pro-inflammatory cytokines, including IL-6 in the lung (Crapo2003). It is unclear, however, whether exposure to CS would lead to an elevated level of IL-6 in the cerebral cortex secondary to oxidative/anti-oxidative imbalance. We have previously found that serum cotinine, an alkaloid found in tobacco that can be used as an indicator for CS exposure and 8-isoprostane were significantly increased; lung superoxide dismutase (SOD) and catalase activity were also elevated as a self-defensive response after 56 days of CS exposure in our established subchronic CS CEP-37440 exposure rat model (Chan et al.2009). SOD is responsible for catalyzing the conversion of superoxide anions into hydrogen peroxide CEP-37440 (Zelko et al.2002) which is further decomposed into water and oxygen by catalase (Chelikani et al.2004). On the other hand, hydrogen peroxide is also removed by the reduced glutathione (GSH) and oxidized glutathione (GSSG) system (Sies1999). Based on our previous findings in the lung, we hypothesized that rat cerebral cortical levels of IL-6 would be increased after CS exposure for 56 days through oxidative pathway. We aimed to determine the cerebral cortical levels of IL-6 and changes in local oxidative/anti-oxidative markers using our established subchronic CS exposure rat model..