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

Allergologie-immunologie - Rhinosinusite chronique avec polypes nasaux : quelle est la place des anticorps monoclonaux en 2020 ? [Chronic rhinosinusitis with nasal polyps : is there a place for monoclonal antibodies in 2020 ?]

Chronic rhinosinusitis with nasal polyps is a severe form of chronic rhinosinusitis, which has a strong negative impact on quality of life. Rhinoscopy is helpful for diagnosis, and initial management depends on intra-nasal corticosteroids and sometimes short-term oral corticosteroids (1 to 3 weeks). If well-conducted drug therapy fails, surgery is considered. In the event of post-surgery recurrence or in case of concomitant severe asthma, biologic therapies represent an interesting option. These drugs include dupilumab, mepolizumab, benralizumab and omalizumab. The choice of medication depends on the individual patient context, which includes the presence of atopic dermatitis, eosinophilia, or asthma

Biologiques et lupus érythémateux systémique : nouveautés et perspectives [Biologics and systemic lupus erythematosous : new insights and perspectives]

Systemic lupus erythematosus is a complex autoimmune disease that remains challenging to treat. Recent advances in the understanding of the pathogenesis of SLE pave the way for the evaluation of biologic medicine. The most promising therapeutic targets in SLE are those that interfere with B cells count or normal function, interferon inhibitors, JAK inhibitors and biologicals that alter the cytokines imbalance that characterizes SLE. Recent phase 3 clinical trials have evaluated the role of belimumab in lupus nephritis and the usefulness of anifrolumab in the treatment of moderate to severe SLE. Many more trials are currently underway and may improve the level of care of patients with SLE in the near future

Lèpre et grossesse : à propos d'un cas et revue de la littérature

Survenue d'une grossesse chez une patiente de 21 ans connue pour lèpre lépromateuse et traitée dès l'âge de 12 ans par trithéraple Intermittente. L'utilisation de la polychimio-thérapie antilépreuse au cours de la grossesse a permis de stabiliser l'évolution de la maladie. L'évolution de la grossesse a été harmonieuse avec naissance à terme d'un nouveau-né cliniquement normal. La grossesse semble favoriser l'évolution de la lèpre. L'utilisation de la polychimiothéraple permet d'en stabiliser l'évolution. Le traitement d'une patiente enceinte est possible et sans risque majeur

EBI2 expression and function: robust in memory lymphocytes and increased by natalizumab in multiple sclerosis

The interaction between oxysterols and the G-protein coupled receptor Epstein-Barr virus induced gene 2 (EBI2) fine tunes immune cell migration, a mechanism efficiently targeted by several disease-modifying treatments developed to treat multiple sclerosis (MS). We previously showed that memory CD4+ T lymphocytes migrate specifically in response to 7α,25-dihydroxycholesterol (7α,25-OHC) via EBI2 in the MS murine model experimental autoimmune encephalomyelitis. However, EBI2 expression profile in human lymphocytes both in healthy and MS donors is unknown. Here, we characterize EBI2 biology in human lymphocytes. We observed that EBI2 is functionally expressed on memory CD4+ T cells and is enhanced under natalizumab treatment, a drug fighting MS by targeting immune cell trafficking. These data suggest a significant role for EBI2 in human CD4+ T cell migration, notably in patients with MS. A better knowledge of EBI2 involvement in autoimmunity may therefore lead to an improved understanding of the physiopathology of MS

Oxysterols regulate CD4+ T cell trafficking during experimental autoimmune encephalomyelitis

Perturbation of steroids pathways has been linked to inflammation and chronic diseases. Oxysterols, oxidised forms of cholesterol, are essential for bile synthesis biosynthesis and sterol transportation. In addition to their basic metabolic properties, oxysterols modulate immune response and control trafficking of immune cells such as B lymphocytes and macrophages. Furthermore, serum oxysterols levels have been proposed as putative candidate biomarkers for neurological diseases such as Multiple sclerosis (MS). The enzyme cholesterol 25 hydroxylase (ch25h) is the rate limiting step to synthetize the oxysterol 7,25-dihydroxycholesterol (725-OHC) from cholesterol. We here report, using the MS murine model experimental autoimmune encephalomyelitis (EAE), that deletion of ch25h attenuated EAE disease course by dampening pathogenic T lymphocytes trafficking to the central nervous system (CNS). While systemic immune response is preserved in the absence of ch25h, IL-17 producing CD4+ T helper (TH17) cells accumulate in the draining lymph nodes. Furthermore, TH17 cells migrate towards 725-OHC in an Epstein-Barr virus-induced G-protein coupled receptor 2 (ebi2) dependent-manner. Collectively, our results reveal a critical involvement for oxysterols in migration of distinct subset of CD4+ T lymphocytes thus supporting a pro-inflammatory role for oxysterols during EAE

Oxysterols regulate encephalitogenic CD4⁺ T cell trafficking during central nervous system autoimmunity

Perturbation of steroids pathways is linked to inflammation and chronic diseases, however the underlying mechanism remains unclear. Oxysterols, oxidized forms of cholesterol, are not only essential for bile synthesis and sterol transportation but have recently been shown to contribute to the immune response. In addition, serum oxysterols levels have been proposed as suitable candidate biomarkers for neurological diseases such as multiple sclerosis (MS). However how oxysterols modulate adaptive immunity is unknown and their functions in autoimmunity have not been investigated. The enzyme cholesterol 25 hydroxylase (Ch25h) is the rate limiting step to synthesize the oxysterol 7α,25-dihydroxycholesterol (7α,25-OHC) from cholesterol. We here report, using the MS murine model experimental autoimmune encephalomyelitis (EAE), that Ch25h deletion significantly attenuated EAE disease course by limiting trafficking of pathogenic CD4(+) T lymphocytes to the central nervous system (CNS). Mechanistically, we show a critical involvement for oxysterols in recruiting leukocytes into inflamed tissues and propose that 7α,25-OHC preferentially promotes the migration of activated CD44(+)CD4(+) T cells by binding the G protein-coupled receptor called Epstein-Barr virus induced gene 2 (EBI2). Collectively, our results support a pro-inflammatory role for oxysterols during EAE and identify oxysterols as a potential therapeutic target to treat autoimmune diseases

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