In the present study we used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model to analyze resveratrol neuroprotective effects. The MPTP-induced PD model is characterized by chronic inflammation, oxidative stress and loss of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). We observed that resveratrol treatment significantly reduced glial activation, decreasing the levels of IL-1β, IL-6 and TNF-α, as well as their respective receptors in the SNpc of MPTP-treated mice, as demonstrated by Western blotting, RT-PCR and quantitative PCR analysis. This reduction is related to possible neuroprotection as we also observed that resveratrol administration limited the decline of tyrosine hydroxylase-immunoreactivity induced in the striatum and SNpc by MPTP injection. Consistent with these data, resveratrol treatment up-regulated the expression of the suppressor of cytokine signaling-1 (SOCS-1), supporting the hypothesis that resveratrol protects DA neurons of the SNpc against MPTP-induced cell loss by regulating inflammatory reactions, possibly through SOCS-1 induction.

Upregulation of inflammatory responses in the brain is associated with a number of neurodegenerative diseases. Microglia are activated in neurodegenerative diseases, producing pro-inflammatory mediators. Critically, lipopolysaccharide (LPS)-induced microglial activation causes dopaminergic neurodegeneration in vitro and in vivo. The signaling mechanisms triggered by LPS to stimulate the release of pro-inflammatory mediators in microglial cells are still incompletely understood. To further explore the mechanisms of LPS-mediated inflammatory response of microglial cells, we studied the role of phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathways known to be activated by toll-like receptor-4 signaling through LPS. In the current study, we report that the activation profile of LPS-induced pAkt activation preceded those of LPS-induced NF-κB activation, suggesting a role for PI3K/Akt in the pathway activation of NF-κB-dependent inflammatory responses of activated microglia. These results, providing the first evidence that PI3K dependent signaling is involved in the inflammatory responses of microglial cells following LPS stimulation, may be useful in preventing inflammatory based neurodegenerative processes.

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Farmed fish are exposed to a continuous antigenic pressure by microbial and environmental agents, which may lead to a condition of chronic inflammation. In view of the notion that polyphenols, largely contained in fruits and vegetables, are endowed with antioxidant and anti-inflammatory activities, farmed sea bass (Dicentrarchus labrax L.) have been administered with red grape polyphenol-enriched feed. Polyphenols were extracted from the seeds of Canosina Nero di Troia Vitis vinifera and mixed with conventional feed at two different concentrations (100 and 200 mg/kg, resp.). Fish samples collected at days 223 and 273, respectively, were evaluated for intestinal and spleen cytokine release as well as for spleen macrophage (MØ) and melanomacrophage center (MMC) areas and distribution. Data will show that in treated fish decrease of intestinal interleukin- (IL-) 1β and IL-6 and increase of splenic interferon- (IFN-) γ occur. On the other hand, in the spleen reduction of MØ number seems to parallel increase in MMCs. Collectively, these data suggest that polyphenol-administered sea bass generate lower levels of intestinal proinflammatory cytokines, while producing larger amounts of spleen IFN-γ, as an expression of a robust and protective adaptive immune response. Increase of MMCs corroborates the evidence for a protective spleen response induced by feed enriched with polyphenols.

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A number of proteins which are needed for the building of new immunodeficiency virus type 1 virions can only be translated from unspliced virus-derived pre-mRNAs. These unspliced mRNAs are shuttled through the nuclear pores reaching the cytosol when bound to the viral protein Rev. However, as a cellular co-factor Rev requires a Rev-binding protein of the AGFG family (nucleoporin-related Arf-GAP domain and FG repeats-containing proteins). In this article we address the evolution of the AGFGs by analyzing the first section of the coding mRNAs. This contains a "core module" which can be traced from Drosophilae to fish, amphibia, birds, and mammals, including man. In the subfamily of AGFG1 molecules the estimated conservation from Drosophilae to primates is 67% (with limited gaps). In some Drosophilae the core module is preceded by a long stretch of more than 300 coding nucleotides, but this additional module is absent in other Drosophilae and in all AGFG1s of other species. The AGFG2 molecules emerged later in evolution, possibly deriving from a duplication of AGFG1s. AGFG2s, present in mammals only, exhibit an additional module of about 50 coding nucleotides ahead of the core module, which is significantly less conserved (54%, with more remarkable gaps). This additional module does not seem to have homologies with the additional module of Drosophilae nor with the precoding section of AGFG1s. Interestingly, in birds a highly re-edited form of the AGFG1 core module (Gallus gallus, Galliformes) coexists with a typical form of the AGFG1 core module (Taeniopygia guttata, Passeriformes).

Giardia intestinalis is a protozoan that causes a generally self-limited clinical illness typically characterized by diarrhea, abdominal cramps, bloating, weight loss and malabsorption. The pathogenesis of giardiasis is multifactorial and probably different in various animal models, but the mechanisms responsible for the disease are still poorly understood. We previously reported that G. intestinalis is able to induce apoptosis in the human HCT-8 epithelial cell line through the activation of both the intrinsic and extrinsic apoptotic pathways. In the present study we demonstrate that activation of the mitogen-activated protein kinases (MAPKs) plays an important role in the regulation of HCT-8 cell apoptosis induced by G. intestinalis. MAPK activation seems to correlate with regulation of the apoptotic process because specific MAPK inhibitors significantly reduced the expression of the active form of caspase-3 in infected cells. Apoptotic changes were also dramatically inhibited by pre-treatment of the cells with JNK or p38 specific inhibitors, but not ERK 1/2 inhibitor. Taken together, these results suggest a critical role for MAPK activation in G. intestinalis-induced apoptosis in the human HCT-8 cell line.