The role of Demodex folliculorum in pathogenesis of rosacea

Introduction and objective: Rosacea is a common chronic inflammatory disease that affects approximately 10% of the population globally. The exact pathogenesis of rosacea remains unknown. However, there are considered several factors such as genetic predisposition, environmental impact, immune dysregulation, as well as presence of microorganisms. The aim of the study is to review recent knowledge about the relationship between rosacea and Demodex folliculorum. The information used in the presented analysis was obtained by searching academic research databases: Google Scholar and PubMed. An abbreviated description of the state of knowledge: Demodex folliculorum is a microscopic mite that resides in the hair follicles and sebaceous glands of the skin. Current studies show that Demodex folliculorum plays an important role in pathogenesis of rosacea. That is related with the induction of excessive pro-inflammatory skin response combined with increase in inflammation mediators. Moreover in patients with rosacea there is observed a nearly 6-fold increase in Demodex folliculorum density in comparison to general population. Increased number of mites is associated with local immunosuppression that may predispose to the development of rosacea. The presence of Demodex mites is related not only with acute course and prolonged duration of the disease, but also with higher probability of recurrence. Summary: Demodex folliculorum is involved in the pathogenesis of rosacea. Moreover, as a parasite, it significantly decreases the quality of patient’s life. Therefore, patients with severe rosacea should be examined for the presence of Demodex mites. In case of detection, regardless of its quantitative load, antiparasitic drug should be recommended.Introduction and objective: Rosacea is a common chronic inflammatory disease that affects approximately 10% of the population globally. The exact pathogenesis of rosacea remains unknown. However, there are considered several factors such as genetic predisposition, environmental impact, immune dysregulation, as well as presence of microorganisms. The aim of the study is to review recent knowledge about the relationship between rosacea and Demodex folliculorum. The information used in the presented analysis was obtained by searching academic research databases: Google Scholar and PubMed. An abbreviated description of the state of knowledge: Demodex folliculorum is a microscopic mite that resides in the hair follicles and sebaceous glands of the skin. Current studies show that Demodex folliculorum plays an important role in pathogenesis of rosacea. That is related with the induction of excessive pro-inflammatory skin response combined with increase in inflammation mediators. Moreover in patients with rosacea there is observed a nearly 6-fold increase in Demodex folliculorum density in comparison to general population. Increased number of mites is associated with local immunosuppression that may predispose to the development of rosacea. The presence of Demodex mites is related not only with acute course and prolonged duration of the disease, but also with higher probability of recurrence. Summary: Demodex folliculorum is involved in the pathogenesis of rosacea. Moreover, as a parasite, it significantly decreases the quality of patient’s life. Therefore, patients with severe rosacea should be examined for the presence of Demodex mites. In case of detection, regardless of its quantitative load, antiparasitic drug should be recommended

Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling

Contains fulltext : 108719.pdf (publisher's version ) (Open Access)BACKGROUND: T lymphocytes are orchestrators of adaptive immunity. Naive T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli and pathway inhibitors. Results from these experiments were validated in a human experimental setting using whole blood and purified CD4+ Tcells. RESULTS: Calcium-dependent activation of T cells using CD3/CD28 and PMA/CD3 stimulation induced a Th1 expression profile reflected by increased expression of T-bet, RUNX3, IL-2, and IFNgamma, whereas calcium-independent activation via PMA/CD28 induced a Th2 expression profile which included GATA3, RXRA, CCL1 and Itk. Knock down with siRNA and gene expression profiling in the presence of selective kinase inhibitors showed that proximal kinases Lck and PKCtheta are crucial signaling hubs during T helper cell activation, revealing a clear role for Lck in Th1 development and for PKCtheta in both Th1 and Th2 development. Medial signaling via MAPkinases appeared to be less important in these pathways, since specific inhibitors of these kinases displayed a minor effect on gene expression. Translation towards a primary, whole blood setting and purified human CD4+ T cells revealed that PMA/CD3 stimulation induced a more pronounced Th1 specific, Lck and PKCtheta dependent IFNgamma production, whereas PMA/CD28 induced Th2 specific IL-5 and IL-13 production, independent of Lck activation. PMA/CD3-mediated skewing towards a Th1 phenotype was also reflected in mRNA expression of the master transcription factor Tbet, whereas PMA/CD28-mediated stimulation enhanced GATA3 mRNA expression in primary human CD4+ Tcells. CONCLUSIONS: This study identifies stimulatory pathways and gene expression profiles for in vitro skewing of T helper cell activation. PMA/CD3 stimulation enhances a Th1-like response in an Lck and PKCtheta dependent fashion, whereas PMA/CD28 stimulation results in a Th2-like phenotype independent of the proximal TCR-tyrosine kinase Lck. This approach offers a robust and fast translational in vitro system for skewed T helper cell responses in Jurkat T cells, primary human CD4+ Tcells and in a more complex matrix such as human whole blood

Monoolein Cubic Phase Gels and Cubosomes Doped with Magnetic Nanoparticles–Hybrid Materials for Controlled Drug Release

Hybrid materials consisting of a monoolein lipidic cubic phase (LCP) incorporating two types of magnetic nanoparticles (NP) were designed as addressable drug delivery systems. The materials, prepared in the form of a gel, were subsequently used as a macroscopic layer modifying an electrode and, after dispersion to nanoscale, as magnetocubosomes. These two LCPs were characterized by small-angle X-ray scattering (SAXS), cross-polarized microscopy, magnetic measurements, and phase diagrams. The magnetic dopants were hydrophobic NP_oleic and hydrophilic NP_citric, characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and their influence on the properties of the cubic phases was investigated. The removal of the anticancer drug, Doxorubicin (Dox) from the hybrid cubic phase gels was studied by electrochemical methods. The advantages of incorporating magnetic nanoparticles into the self-assembled lipid liquid crystalline phases include the ability to address the cubic phase nanoparticle containing large amounts of drug and to control the kinetics of the drug release

Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity

The purpose of the study was to examine the potential of inhibition of cathepsin S as a treatment for autoimmune diseases. A highly selective cathepsin S inhibitor, CSI-75, was shown to upregulate levels of the cathepsin S substrate, invariant chain Lip10, in vitro as well as in vivo in C57Bl/6 mice after oral administration. Functional activity of the compound was shown by a reduction in the OVA-specific response of OVA-sensitized splenocytes from C57Bl/6 mice as well as from OVA-TCR transgenic mice (DO11.10). Since these studies revealed a selective suppression of the Th1 and Th17 cytokines causing a shift to Th2, CSI-75 was tested in the murine HC-gp39-immunization model. Indeed, CSI-75 specifically reduced the circulating HC-gp39-specific IgG2a in these mice indicating selective inhibition of the Th1 type of response in vivo. The importance of especially the Th1 and Th17 cell subsets in the pathology of autoimmune diseases, renders CatS inhibition a highly interesting potential therapeutic treatment of autoimmune diseases. Therefore, CSI-75 was tested in a murine model of multiple sclerosis (i.e. experimental autoimmune encephalomyelitis (EAE)) in a semi-therapeutic setting (ie. oral treatment after initial sensitization to antigen). Finally, in a murine model with features resembling rheumatoid arthritis (the collagen-induced arthritis (CIA) model), CSI-75 was tested in a therapeutic manner (after disease development). CSI-75 caused a significant reduction in disease score in both disease models, indicating a promising role for CatS inhibitors in the area of therapeutic treatments for autoimmune diseases. (C) 2011 Published by Elsevier Ltd