Resveratrol Inhibits Inflammatory Responses via the Mammalian Target of Rapamycin Signaling Pathway in Cultured LPS-Stimulated Microglial Cells

Resveratrol have been known to possess many pharmacological properties including antioxidant, cardioprotective and anticancer effects. Although current studies indicate that resveratrol produces neuroprotection against neurological disorders, the precise mechanisms for its beneficial effects are still not fully understood. We investigate the effect of anti-inflammatory and mechamisms of resveratrol by using lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells.BV-2 cells were treated with resveratrol (25, 50, and 100 µM) and/or LPS (1 µg/ml). Nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by Griess reagent and ELISA. The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR and double immunofluorescence labeling, respectively. Phosphorylation levels of PTEN (phosphatase and tensin homolog deleted on chromosome 10), Akt, mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) cascades, inhibitor κB-α (IκB-α) and cyclic AMP-responsive element-binding protein (CREB) were measured by western blot. Resveratrol significantly attenuated the LPS-induced expression of NO, PGE2, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nuclear factor-κB (NF-κB) in BV-2 cells. Resveratrol increased PTEN, Akt and mTOR phosphorylation in a dose-dependent manner or a time-dependent manner. Rapamycin (10 nM), a specific mTOR inhibitor, blocked the effects of resveratrol on LPS-induced microglial activation. In addition, mTOR inhibition partially abolished the inhibitory effect of resveratrol on the phosphorylation of IκB-α, CREB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK).This study indicates that resveratrol inhibited LPS-induced proinflammatory enzymes and proinflammatory cytokines via down-regulation phosphorylation of NF-κB, CREB and MAPKs family in a mTOR-dependent manner. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of resveratrol

Cell type specificity of female lung cancer associated with sulfur dioxide from air pollutants in Taiwan: An ecological study

<p>Abstract</p> <p>Background</p> <p>Many studies have examined the association between air pollutants (including sulfur dioxide [SO₂], carbon monoxide [CO], nitrogen dioxide [NO₂], nitric oxide [NO], ozone [O₃], and particulate matter < 10 μm [PM₁₀]) and lung cancer. However, data from previous studies on pathological cell types were limited, especially for SO₂exposure. We aimed to explore the association between SO₂exposure from outdoor air pollutants and female lung cancer incidence by cell type specificity.</p> <p>Methods</p> <p>We conducted an ecological study and calculated annual average concentration of 6 air pollutants (SO₂, CO, NO₂, NO, O₃, and PM₁₀) using data from Taiwan Environmental Protection Administration air quality monitoring stations. The Poisson regression models were used to evaluate the association between SO₂and age-standardized incidence rate of female lung cancer by two major pathological types (adenocarcinoma [AC] and squamous cell carcinoma [SCC]). In order to understand whether there is a dose-response relationship between SO₂and two major pathological types, we analyzed 4 levels of exposure based on quartiles of concentration of SO₂.</p> <p>Results</p> <p>The Poisson regression results showed that with the first quartile of SO₂concentration as the baseline, the relative risks for AC/SCC type cancer among females were 1.20 (95% confidence interval [CI], 1.04-1.37)/1.39 (95% CI, 0.96-2.01) for the second, 1.22 (95% CI, 1.04-1.43)/1.58 (95% CI, 1.06-2.37) for the third, and 1.27 (95% CI, 1.06-1.52)/1.80 (95% CI, 1.15-2.84) for the fourth quartile of SO₂concentration. The tests for trend were statistically significant for both AC and SCC at <it>P = </it>0.0272 and 0.0145, respectively.</p> <p>Conclusion</p> <p>The current study suggests that SO₂exposure as an air pollutant may increase female lung cancer incidence and the associations with female lung cancer is much stronger for SCC than for AC. The findings of this study warrant further investigation on the role of SO₂in the etiology of SCC.</p

MyD88 and Src Are Differentially Regulated in Kupffer Cells of Males and Proestrus Females Following Hypoxia

Hypoxia produces sex dimorphic immune responses in males and proestrus females. Because Kupffer cells are the major source of proinflammatory cytokines, studies were conducted to discern IL-6 production in mouse Kupffer cells following hypoxia. Hypoxia enhances TLR4 expression in Kupffer cells irrespective of sex. However, MyD88 and Src expression in Kupffer cells decreased significantly after hypoxia in proestrus females, whereas Src protein expression and phosphorylation increased in males in concurrence with differences in IL-6 production. 17β-Estradiol administration elevated MyD88 and Src expression in males to levels in normoxic proestrus females. Administration of Src inhibitor in hypoxic males prevented increased IL-6 production. Thus, differential regulation of MyD88 and Src in males and females plays an important role in sex-specific immune response following hypoxia

Characteristics of adenovirus vectors

Adenovirus vectors have shown seductive promise as molecular biology tools and are being proposed for a number of clinical gene delivery applications. We will review the properties of adenovirus vectors that are responsible for the great interest in their use. We will discuss a number of the limitations of the current vectors and describe some of the strategies that are being used to improve these vectors