Local anesthetics (LAs) inhibit membrane depolarization by reducing sodium and potassium conductance, and subsequent displacement of calcium ions from binding sites seems to occur. Histamine release appears to be a secretory process in which calcium couples the stimulus to the exocytosis of histamine-containing granules. Furthermore, LAs are structurally similar to histamine H(1)-receptor antag...

Interleukin-26 (IL-26), a member of the IL-10 cytokine family, induces the production of proinflammatory cytokines by epithelial cells. IL-26 has been also reported overexpressed in Crohn's disease, suggesting that it may be involved in the physiopathology of chronic inflammatory disorders. Here, we have analyzed the expression and role of IL-26 in rheumatoid arthritis (RA), a chronic inflammat...

IL-17-producing CD4 T cells play a key role in immune responses against extracellular bacteria and autoimmunity. Nuclear factor κB (NF-κB) is required for T-cell activation and selected effector functions, but its role in Th17 differentiation is controversial. Using genetic mouse models that impede T-cell-NF-κB signaling either downstream of the T-cell receptor (TCR) or of IκB kinase β (IKKβ), ...

Cytokines orchestrate the tumor-promoting interplay between malignant cells and the immune system. In many experimental and human cancers, the cytokine TNF-alpha is an important component of this interplay, but its effects are pleiotropic and therefore remain to be completely defined. Using a mouse model of ovarian cancer in which either TNF receptor 1 (TNFR1) signaling was manipulated in diffe...

BACKGROUND Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with an unclear etiology. This study aims to investigate the role of IL-23/Th17 pathway in patients with ITP. METHOD The gene expressions of IL-17, IL-23 and their receptors in ITP patients and healthy controls were analyzed by quantitative real-time PCR. ELISA was used to test the IL-17 and IL-23 levels in pl...

Elevated levels of proinflammatory cytokines associated with infection and inflammation can modulate cytochrome P450 enzymes, leading to potential disease-drug interactions and altered small-molecule drug disposition. We established a human-derived hepatocyte-Kupffer cell (Hep:KC) coculture model to assess the indirect cytokine impact on hepatocytes through stimulation of KC-mediated cytokine r...

Although(,) vascular remodeling is a hallmark of many chronic inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, anti-vascular strategies to treat these conditions have received little attention to date. We investigated the anti-inflammatory activity of systemic blockade of VEGF-A by the inhibitory monoclonal antibody G6-31, employing a therapeutic t...

1. Ayyoub M, Raffin C, Valmori D. Generation of Th17 from human naive CD4 T cells preferentially occurs from FOXP3 Tregs upon costimulation via CD28 or CD5 [letter]. Blood. 2012;119(20):4810-4812. 2. de Wit J, Souwer Y, van Beelen AJ, et al. CD5 costimulation induces stable Th17 development by promoting IL-23R expression and sustained STAT3 activation. Blood. 2011;118(23):6107-6114. 3. Zhou L, ...

The de novo generation of Foxp3+ regulatory T (Treg) cells in the peripheral immune compartment and the differentiation of Th17 cells both require TGF-beta, and IL-6 and IL-21 are switch factors that drive the development of Th17 cells at the expense of Treg cell generation. The major vitamin A metabolite all-trans retinoic acid (RA) not only enforces the generation of Treg cells but also inhib...

Two new spiranoid withanolides, (20R,22R,23R)-12β ,17β ,22-trihydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (3) and (23R)-5α ,6β ,12β ,21-tetrahydroxy-1,22-dioxo-12,23-cycloergosta-2,17,24-trien-26,23-olide (4) were isolated from plants of Jaborosa odonelliana and Jaborosa runcinata, respectively. Compounds 3 and 4 were characterized by a combination of spectroscopic methods (1D and 2D...