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α-Synuclein is known to be a major component of Lewy bodies and glial cytoplasmic inclusions in the brains of patients with α-synucleinopathies. Synphilin-1, an α-synuclein-associated protein, is also present in these inclusions. However, little is known about the post-translational modifications of synphilin-1. In the present study, it is reported that synphilin-1 is phosphorylated by glycogen synthase kinase-3βin vitro . It is well known that protein phosphorylation is involved in various physiological phenomena, including signal transduction and protein degradation. Therefore, phosphorylation of synphilin-1 may play an important role in the function of this protein in the brain. [ABSTRACT FROM AUTHOR]

Background: Galectin-9 is involved in chemotaxis and adhesion of eosinophils, and is induced in vascular endothelial cells by interferon-γ (IFN-γ). 15-Deoxy-Δ[sup 12,14] -prostaglandin J[sub 2] (15d-PGJ[sub 2] ) is a ligand for peroxisome proliferator-activated receptor-γ (PPAR-γ), and known to modulate the expression of various genes. Methods: We have studied the effect of 15d-PGJ[sub 2] on the IFN-γ-induced galectin-9 expression in human umbilical vein endothelial cells (HUVEC) in culture. Results: 15d-PGJ[sub 2] inhibited the IFN-γ-induced galectin-9 expression in a PPAR-γ-independent manner, and also inhibited the adhesion of EoL-1 cells to an HUVEC monolayer treated with IFN-γ. 15d-PGJ[sub 2] partially inhibited IFN-γ-induced phosphorylation of STAT-1 in HUVEC. Conclusions: 15d-PGJ[sub 2] may regulate inflammatory reactions through the inhibition of galectin-9 expression.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary Peroxisome proliferator-activated receptor-γ (PPAR-γ)is a member of nuclear hormone receptor superfamily, and is knownto play a role in various biological processes including inflammatoryresponses and adipocyte differentiation. CX3CL1/fractalkineis a potent agonist for chemotaxis and adhesion of monocytes and lymphocytes.Endothelial cells produce fractalkine when stimulated with cytokinessuch as interleukin-1 (IL-1), tumour necrosis factor-α andinterferon-γ (IFN-γ). We herein report that 15-deoxy-n12,14 -prostaglandinJ2 (15d-PGJ2 ), a PPAR-γ agonist,inhibits the expression of fractalkine induced by IFN-γ orIL-1β in human endothelial cells. Agonist for PPAR-α (WY14643)or PPAR-γ (ciglitazone) did not inhibit the cytokine-inducedfractalkine expression, and the effect of 15d-PGJ2 maybe independent of PPAR. 15-Deoxy- D12,14 prostaglandinJ2 also inhibited the adhesion of blood mononuclear cellsto endothelial monolayers treated with IFN-γ or IL-1β.The data suggest that 15d-PGJ2 regulates inflammatoryreactions, at least in part, through the inhibition of fractalkineexpression and leucocyte traffic through the endothelium. [ABSTRACT FROM AUTHOR]

α-Synuclein was originally identified as the presynaptic nerve terminal protein. Recently, we reported that α-synuclein is also expressed in cultured human astrocytes and that its levels are increased by stimulation with interleukin-1β, suggesting that it may be involved in inflammatory processes. We therefore investigated the effect of inflammatory stimuli on α-synuclein expression in human macrophages. α-Synuclein mRNA and protein were detected in cultured human macrophages and levels of α-synuclein protein were increased by stimulation with lipopolysaccharide and interleukin-1β in a time- and concentration-dependent manner. Immunofluorescent staining showed that α-synuclein protein was expressed within the cytoplasm and nucleus. Furthermore, α-synuclein immunoreactivity was present in alveolar macrophages from human lung tissues. These findings suggest that the function of α-synuclein is not exclusive to the nervous system and that α-synuclein may play a role in inflammatory processes and immune responses. [ABSTRACT FROM AUTHOR]

Summary Interleukin-6 (IL-6) is a multifunctional cytokine that plays an important role in inflammatory reactions. We have addressed the possible regulation of IL-6 expression by the ubiquitin-protease system in human umbilical vein endothelial cells. Cultured endothelial cells were treated with MG-132, a protease inhibitor, and the levels of IL-6 mRNA and protein were measured by reverse transcription-PCR and ELISA. MG-132 increased the expression of IL-6 mRNA and protein; and this effect was abolished by the pretreatment of the cells with U0126, an inhibitor of MAP or ERK kinases (MEK1/2). MG-132 treatment was also found to enhance the level of phosphorylated MEK1/2. Treatment of the cells with actinomycin D inhibited IL-6 expression in response to MG-132, suggesting the transcriptional upregulation of IL-6 under proteasomal inhibition. We conclude that a protease inhibitor MG-132 upregulates IL-6 expression in vascular endothelial cells, at least in part, through the activation of MEK1/2. [ABSTRACT FROM AUTHOR]