Viscum album Exerts Anti-Inflammatory Effect by Selectively Inhibiting Cytokine-Induced Expression of Cyclooxygenase-2

Viscum album (VA) preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2) and prostaglandin E2 (PGE2) play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells) as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez) for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

When obstetrics-gynecology specialists need to call an ophthalmologist urgently: a case report.

We report here a case of a healthy 23-year-old female patient who was assessed at the gynecology emergency department for genital ulcers, fever, and blurred vision. After suspicion of herpes simplex virus-2 lesions, the diagnosis of Behçet's disease was made. We report this case with the aim of including Behçet's disease in the differential diagnosis of genital ulcers, and emphasize the emergency of the vision loss that can be irreversible. A healthy 23-year-old European female patient was assessed by gynecology in the emergency department for genital lesions associated with fever and blurred vision. At first, these lesions were suspected to be primary herpes simplex virus-2 infection One day later, she experienced decreased visual acuity in both eyes. After 4 days of worsening genital ulcers and persistent blurred vision, the patient was referred to the ophthalmology department. Fundoscopic examination showed retinal hemorrhages that were consistent with the first presentation of Behçet's disease. This case demonstrates that genital ulcers can be the very initial symptom of this ophthalmologic emergency. The differential diagnosis of genital ulcers is challenging. Behçet's disease should be included, especially when associated with systemic or ocular manifestations, and should be considered an emergency for the gynecologist to prevent long-term vision loss

IL-27-Induced Type 1 Regulatory T-Cells Produce Oxysterols that Constrain IL-10 Production

IF 6.429International audienceThe behaviors of lymphocytes, including CD4(+) T helper cells, are controlled on many levels by internal metabolic properties. Lipid metabolites have recently been ascribed a novel function as immune response modulators and perturbation of steroids pathways modulates inflammation and potentially promotes a variety of diseases. However, the impact of lipid metabolism on autoimmune disease development and lymphocyte biology is still largely unraveled. In this line, oxysterols, oxidized forms of cholesterol, have pleiotropic roles on the immune response aside from their involvements in lipid metabolism. The oxysterols 25-hydroxycholesterol (25-OHC) and 7α,25-dihydroxycholesterol (7α,25-OHC) regulate antiviral immunity and immune cell chemotaxis. However, their physiological effects on adaptive immune response in particular on various subset CD4(+) T lymphocytes are largely unknown. Here, we assessed oxysterol levels in subset of CD4(+) T cells and demonstrated that 25-OHC and transcript levels of its synthesizing enzyme, cholesterol 25-hydroxylase, were specifically increased in IL-27-induced type 1 regulatory T (TR1) cells. We further showed that 25-OHC acts as a negative regulator of TR1 cells in particular of IL-10 secretion via liver X receptor signaling. Not only do these findings unravel molecular mechanisms accounting for IL-27 signaling but also they highlight oxysterols as pro-inflammatory mediators that dampens regulatory T cell responses and thus unleash a pro-inflammatory response

A single nucleotide polymorphism in the gene for GPR183 increases its surface expression on blood lymphocytes of patients with inflammatory bowel disease.

The single nucleotide polymorphism rs9557195 within the gene Epstein-Barr virus-induced G protein-coupled receptor 2 (EBI2) has been associated with increased risk for inflammatory bowel diseases (IBD). EBI2 mediates migration of intestinal immune cells and promotes colitis in animal models. Here we study EBI2 surface expression of immune cells and associations of rs9557195 with EBI2 expression and IBD disease course. We recruited 27 IBD patients (15 with ulcerative colitis (UC), 12 with Crohn's disease (CD)), and 8 healthy volunteers (HV). EBI2 expression was measured by fluorescence activated cell sorting in subtypes of peripheral blood mononuclear cells. We further analyzed IBD disease course in 2301 patients (1335 with CD and 966 with UC) of the Swiss IBD cohort study (SIBDCS). We found increased EBI2 expression in lymphocytes expressing chemokine receptors CCR6 or CCR9, implicated in IBD and on Th17 memory T cells. The EBI2 ligand 7α,25-dihydroxycholesterol and the CCR6 ligand CCL20 stimulated migration of memory T cells in an additive manner. Further, IBD patients with the CC allele of rs9557195 had higher EBI2 surface expression compared to individuals with the TT allele. SIBDC patients carrying the rs9557195-CC allele had higher psoriasis rates compared to individuals with the TT allele. We demonstrate increased EBI2 surface expression on T cells with a potential role in gut inflammation. A SNP of the EBI2 locus was associated with EBI2 surface expression and psoriasis rates in IBD patients. Our data suggest a pro-inflammatory role of EBI2 in IBD

A single nucleotide polymorphism in the gene for GPR183 increases its surface expression on blood lymphocytes of patients with inflammatory bowel disease

Background and purpose: Single nucleotide polymorphism rs9557195 within the gene of the G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2/GPR183) has been associated with increased risk for inflammatory bowel diseases (IBD). GPR183 mediates the migration of intestinal immune cells and promotes colitis in animal models. Here, we study GPR183 surface expression of immune cells and associations of rs9557195 with GPR183 expression and IBD disease course. Experimental approach: We recruited 27 IBD patients (15 with ulcerative colitis [UC] and 12 with Crohn's disease [CD]) and eight healthy volunteers (HV). GPR183 expression was measured by FACS in subtypes of peripheral blood mononuclear cells. We analysed IBD disease course in 2301 patients (1335 with CD and 966 with UC) of the Swiss IBD cohort study. Key results: We found increased GPR183 expression in lymphocytes expressing chemokine receptors CCR6 or CCR9, implicated in IBD and on Th17 memory T cells. The GPR183 ligand 7α,25-dihydroxycholesterol and the CCR6 ligand CCL20 stimulated migration of memory T cells in an additive manner. Further, IBD patients with the CC allele of rs9557195 had higher GPR183 surface expression compared to individuals with the TT allele. Swiss IBD cohort study patients carrying the rs9557195-CC allele had higher psoriasis rates compared to individuals with the TT allele. Conclusion and implications: We demonstrate increased GPR183 surface expression on T cells with a potential role in gut inflammation. An SNP of the GPR183 locus was associated with GPR183 surface expression and psoriasis rates in IBD patients. Our data suggest a pro-inflammatory role of GPR183 in IBD. Linked articles: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc. Keywords: FACS; GPR183/EBI2; IBD; SNP; UBAC2; psoriasis