The influence of excessive IL-6 production in vivo on the development and function of Foxp3+ regulatory T cells.

IL-6 is a proinflammatory cytokine and its overproduction is implicated in a variety of inflammatory disorders. Recent in vitro analyses suggest that IL-6 is a key cytokine that determines the balance between Foxp3(+) regulatory T cells (Tregs) and Th17 cells. However, it remains unclear whether excessive IL-6 production in vivo alters the development and function of Foxp3(+) Tregs.

Down-regulation of hepcidin resulting from long-term treatment with an anti-IL-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric Castleman disease.

Dysregulated production of hepcidin is implicated in anemia of inflammation, whereas interleukin-6 (IL-6) is a major inducer of hepcidin production. Overproduction of IL-6 is responsible for pathogenesis of multicentric Castleman disease (MCD), a rare lymphoproliferative disorder accompanied by systemic inflammatory responses and anemia. In this study, we investigated the roles of hepcidin and IL-6 in anemia of inflammation and the long-term effects of anti-IL-6 receptor antibody (tocilizumab) treatment on serum hepcidin and iron-related parameters in MCD patients.

Green tea polyphenol epigallocatechin gallate inhibits cell signaling by inducing SOCS1 gene expression.

Therapeutic effects of green tea involve an inhibitory function of its constituent polyphenol epigallocatechin gallate (EGCG) on cell signaling. The specificity and mechanism(s) by which EGCG inhibits cell signaling have remained unclear. Here, we demonstrate that green tea and EGCG induce suppressor of cytokine signaling 1 (SOCS1) gene expression, a negative regulator of specific cell signaling pathways.

iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases.

Objective: To identify a novel serum biomarker of disease activity in inflammatory autoimmune disorders.

Methods: Sera obtained from rheumatoid arthritis (RA) patients before and after anti-TNF therapy were analysed by iTRAQ (isobaric tags for relative and absolute quantitation) quantitative proteomic analysis and further validated by ELISA.

Results: Of 326 proteins identified by proteomic analysis, increased serum levels of leucine-rich alpha-2 glycoprotein (LRG) was identified in RA patients before therapy.

Interleukin-6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses.

Objective: To investigate the mechanism of interleukin-6 (IL-6) blockade in autoimmune arthritis, by comparing the effect of anti-IL-6 receptor (anti-IL-6R) monoclonal antibody (mAb) treatment with the effect of soluble tumor necrosis factor (sTNFR)-Fc fusion protein treatment on T helper cell differentiation in collagen-induced arthritis (CIA).

Methods: DBA/1 mice were immunized with type II collagen (CII) to induce arthritis and were left untreated or were treated with anti-IL-6R mAb or TNFR-Fc. T helper cell differentiation and cytokine expression during the development of arthritis in these mice were analyzed.

IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis.

The development of Th17 cells is a key event in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis (MS). Previous studies have demonstrated that an IL-6-dependent pathway is involved in the differentiation of Th17 cells from naïve CD4-positive T cells in vitro. However, the role of IL-6 in vivo in the development of Th17 cells in EAE has remained unclear.

Transcriptional complex formation of c-Fos, STAT3, and hepatocyte NF-1 alpha is essential for cytokine-driven C-reactive protein gene expression.

C-reactive protein (CRP) is a sensitive marker and mediator of inflammation, whereas IL-6 blocking therapy can normalize serum levels of CRP in chronic inflammatory diseases. We investigated the precise synergistic induction mechanism of CRP gene expression by IL-1 and IL-6 in Hep3B cells. In the early induction phase, IL-1 inhibited IL-6-mediated CRP gene expression, and NF-kappaB p65 inhibited the luciferase activity of pGL3-CRP by IL-1 plus IL-6 even in the presence of overexpressed STAT3.

Fully automated liquid chromatography-mass spectrometry determination of 17beta-estradiol in river water.

Surface modified molecularly imprinted polymers (SM-MIPs) for 17beta-estradiol (E2), utilizing 6-ketoecradiol as a pseudo template were prepared. MIPs for E2 were synthesized using 4-vinyl pyridine and ethylene dimethacrylate as a functional monomer and cross-linking agent, respectively. MIPs selectively retained E2 and provided excellent chromatographic resolution from interfering compounds inherent in river water sample matrices.

Essential role of STAT3 in cytokine-driven NF-kappaB-mediated serum amyloid A gene expression.

Serum amyloid A (SAA) is a sensitive marker of acute-phase responses and known as a precursor protein of amyloid fibril in amyloid A (AA) (secondary) amyloidosis. Since the serum SAA level is also closely related to activity of chronic inflammatory disease and coronary artery disease, it is important to clarify the exact induction mechanism of SAA from the clinical point of view. Here we provide evidence that STAT3 plays an essential role in cytokine-driven SAA expression, although the human SAA gene shows no typical STAT3 response element (RE) in its promoters.

IL-6 plays a critical role in the synergistic induction of human serum amyloid A (SAA) gene when stimulated with proinflammatory cytokines as analyzed with an SAA isoform real-time quantitative RT-PCR assay system.

Serum amyloid A (SAA) is known to be a precursor of amyloid A (AA) protein in AA (secondary) amyloidosis and SAA1 to be mainly involved in AA amyloidosis. We established an SAA isoform real-time quantitative RT-PCR assay and found that beta-2 microglobulin is more stable as an internal control than GAPDH and beta-actin for our system. Either IL-6 and IL-1beta or IL-6 and TNFalpha, but not IL-1beta and TNFalpha, induced the synergistic induction of SAA1 and SAA2 genes.

Isolation and characterization of Saccharomyces cerevisiae genes differentially expressed under different growth conditions.

The budding yeast Saccharomyces cerevisiae, like many other microorganisms, responds to nutrient starvation by arresting growth and entering into a non-proliferating stationary phase. Studies on the response of S. cerevisiae cells to growth arrest might provide further insight into the non-proliferative states of cells in multi-cellular eukaryotic organisms.