Alterations of the host response caused by short-term exposure to high levels of smoke during the act of smoking (acute smoke exposure) as well as long-term exposure to lower levels of tobacco substances in the bloodstream of smokers (chronic smoke exposure) may play a role in the pathogenesis of periodontal diseases in smokers. In this study, we examined the secretion of three cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta] from mononuclear blood cells from current smokers and non-smokers exposed to in vitro tobacco smoke (which may be comparable to in vivo acute smoke exposure) and mononuclear blood cells from current smokers not exposed to further in vitro smoke (which may be comparable to chronic smoke exposure). Peripheral blood mononuclear cells were isolated from eight healthy current smokers and eight healthy non-smokers, plated in culture wells, exposed in vitro for 1-5 min to cigarette smoke in a smoke box system or not exposed (baseline controls), and then incubated without further smoke exposure for another 24 h. Supernatants from each well were then collected and assayed for the concentrations of the three cytokines by enzyme-linked immunosorbent assay (ELISA). At baseline, mean IL-1beta levels were higher in smokers than in non-smokers (mean: 10.6 vs. 5.9 pg/ml, anova: P < 0.05). In both smokers and non-smokers, secreted levels of IL-1beta increased from 0 to 5 min of in vitro smoke exposure (mean: 5.9-9.9 pg/ml, t-test: P < 0.05 for non-smokers only) with levels in smokers higher than in non-smokers (P > 0.05). Mean TNF-alpha levels increased from 0 to 2 min of smoke exposure and decreased from 2 to 5 min in smokers and non-smokers, with higher levels in non-smokers than smokers at all time-points (P > 0.05). Mean TGF-beta levels were higher in smokers than in non-smokers at all time-points (mean: 180.5 vs. 132.0 pg/ml, P < 0.05 at 5 min only) with no significant alteration of the pattern of secretion with cigarette smoke exposure. These observed alterations in the secretion of cytokines from mononuclear blood cells in smokers, relative to non-smokers, and with in vitro smoke exposure may play a role in the pathogenesis of periodontal diseases in smokers.
Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study investigated the role of Nrf2 in modulating traumatic brain injury (TBI)-induced secondary brain injury. Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. The absence of Nrf2 function in mice resulted in exacerbated brain injury as shown by the increased severity of neurological deficit, apoptosis, and brain edema at 24h after TBI. This exacerbation of brain injury in Nrf2-deficient mice was associated with increased mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), and with decreased mRNA expression and enzymatic activity of antioxidant and detoxifying enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha-1 (GST-alpha1), compared with their wild-type counterparts after TBI. In combination, these results suggest that Nrf2 plays an important role in protecting TBI-induced secondary brain injury, possibly by regulating inflammatory cytokines and inducing antioxidant and detoxifying enzymes.
We have previously shown that traumatic brain injury (TBI) can induce an upregulation of nuclear factor kappa B (NF-κB) and proinflammatory cytokines in the gut, which play an important role in the pathogenesis of acute gut mucosal injury mediated by inflammation. In this work, we investigated whether progesterone administration modulated intestinal NF-κB activity and proinflammatory cytokines expression after TBI in male rats. As a result, we found that administration of progesterone following TBI could decrease NF-κB binding activity, NF-κB p65 protein expression, and concentrations of interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the gut. TBI-induced damages of gut structure were ameliorated after progesterone injections. The results of the present study suggest that the therapeutic benefit of post-TBI progesterone injections might be due to its inhibitory effects on intestinal NF-κB activation and proinflammatory cytokines expression.
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