50 research outputs found
P38 MAPK signaling in pemphigus: Implications for skin autoimmunity
No full textp38 mitogen activated protein kinase (p38 MAPK) signaling plays a major role in the modulation of immune-mediated inflammatory responses and therefore has been linked with several autoimmune diseases. The extent of the involvement of p38 MAPK in the pathogenesis of autoimmune blistering diseases has started to emerge, but whether it pays a critical role is a matter of debate. The activity of p38 MAPK has been studied in great detail during the loss of keratinocyte cell-cell adhesions and the development of pemphigus vulgaris (PV) and pemphigus foliaceus (PF). These diseases are characterised by autoantibodies targeting desmogleins (Dsg). Whether autoantibody-antigen interactions can trigger signaling pathways (such as p38 MAPK) that are tightly linked to the secretion of inflammatory mediators which may perpetuate inflammation and tissue damage in pemphigus remains unclear. Yet, the ability of p38 MAPK inhibitors to block activation of the proapoptotic proteinase caspase-3 suggests that the induction of apoptosis may be a consequence of p38 MAPK activation during acantholysis in PV. This review discusses the current evidence for the role of p38 MAPK in the pathogenesis of pemphigus. We will also present data relating to the targeting of these cascades as a means of therapeutic intervention. © 2013 Athanasios Mavropoulos et al
The Role of Invariant NKT in Autoimmune Liver Disease: Can Vitamin D Act as an Immunomodulator?
No full textNatural killer T (NKT) cells are a distinct lineage of T cells which express both the T cell receptor (TCR) and natural killer (NK) cell markers. Invariant NKT (iNKT) cells bear an invariant TCR and recognize a small variety of glycolipid antigens presented by CD1d (nonclassical MHC-I). CD1d-restricted iNKT cells are regulators of immune responses and produce cytokines that may be proinflammatory (such as interferon-gamma (IFN-γ)) or anti-inflammatory (such as IL-4). iNKT cells also appear to play a role in B cell regulation and antibody production. Alpha-galactosylceramide (α-GalCer), a derivative of the marine sponge, is a potent stimulator of iNKT cells and has been proposed as a therapeutic iNKT cell activator. Invariant NKT cells have been implicated in the development and perpetuation of several autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus (SLE). Animal models of SLE have shown abnormalities in iNKT cells numbers and function, and an inverse correlation between the frequency of NKT cells and IgG levels has also been observed. The role of iNKT cells in autoimmune liver disease (AiLD) has not been extensively studied. This review discusses the current data with regard to iNKT cells function in AiLD, in addition to providing an overview of iNKT cells function in other autoimmune conditions and animal models. We also discuss data regarding the immunomodulatory effects of vitamin D on iNKT cells, which may serve as a potential therapeutic target, given that deficiencies in vitamin D have been reported in various autoimmune disorders
Stereoselective intermolecular oxymercurations of allylic ethers.
No full textThe influence of alkene geometry and allylic substitution on the stereochemical outcome of intermolecular oxymercurations of allylic ethers is described. (C) 1997 Published by Elsevier Science Ltd.PT: J; CR: BRATT K, 1996, J ORG CHEM, V61, P2109 CHAMBERLIN AR, 1984, TETRAHEDRON, V40, P2297 EVANS DA, 1990, J AM CHEM SOC, V112, P7001 FUJIOKA H, 1993, HETEROCYCLES, V35, P665 GARAVELAS A, 1995, TETRAHEDRON LETT, V36, P463 GIESE B, 1985, TETRAHEDRON LETT, V26, P1197 MAVROPOULOS I, 1996, TETRAHEDRON LETT, V37, P3751; NR: 7; TC: 3; J9: TETRAHEDRON LETT; PG: 4; GA: WT464Source type: Electronic(1
In search of common ground: How can Eastern Orthodox theology develop a natural law theory?
No full textWhile natural law theory plays an important role for Catholic moral theology, it is true that
Orthodox ethics has not endeavoured to develop its own theory of natural law. This article
demonstrates the existence of the concept of natural law in Eastern Orthodox theology and
argues that the main reason for this neglect is Eastern Christianity’s traditional focus on faith
rather than reason. In addition, the author, based on biblical and patristic grounds, highlights
the necessity for a balance between the two to be found and provides a way in which
Orthodox moral theology could develop a natural law theory, should it ever feel the need to
do so, by first redefining its relationship with the science of philosophy, after so many years of
disregard
The Role of Flavonoids in Inhibiting Th17 Responses in Inflammatory Arthritis
No full textFlavonoids have been considered powerful anti-inflammatory agents, and their exact immunomodulatory action as therapeutic agents in autoimmune diseases has started to emerge. Their role in the manipulation of immunoregulation is less understood. Several studies attempted to investigate the role of various flavonoids mainly in experimental models of autoimmune diseases, especially in the context of their potential effect on the increase of regulatory T cells (Tregs) and their ability to stimulate an overexpression of anti-inflammatory cytokines, in particular that of IL-10. The emergence of IL-17, a cytokine largely produced by Th17 cells, as a powerful proinflammatory stimulus which attenuates the induction of Tregs has prompted a series of studies investigating the role of flavonoids on Th17 cells in experimental models as well as human autoimmune diseases. This review thoroughly discusses accumulated data on the role of flavonoids on Th17 in rheumatoid arthritis and experimental autoimmune arthritis
Human Peripheral Blood Mononuclear Cell Culture for Flow Cytometric Analysis of Phosphorylated Mitogen-Activated Protein Kinases
No full textComparison of the effect of the aerobic glycolysis inhibitor dichloroacetate and of the Krebs cycle inhibitor LW6 on cellular and humoral alloimmunity
No full textPhosphodiesterase 4 Inhibitors in Immune-mediated Diseases: Mode of Action, Clinical Applications, Current and Future Perspectives
No full textStabilization of IFN-γ mRNA by MAPK p38 in IL-12- and IL-18-stimulated human NK cells
No full textThe rapid induction of interferon-γ (IFN-γ) by innate cytokines such as interleukin 12 (IL-12) and IL-18 is critical for immunity against infectious pathogens. We investigated the molecular mechanisms underlying this response. IL-12 and IL-18 rapidly and synergistically induced the secretion of IFN-γ by freshly purified human peripheral blood lymphocytes. At early time points, IFN-γ was expressed almost exclusively by natural killer cells and in both CD56brlght and CD56dlm subpopulations. Mitogen-activated protein kinase p38 was activated strongly by IL-18 and weakly by IL-12 in natural killer cells but was not activated by either cytokine in T cells. The expression of IFN-γ mRNA and protein was dose-dependently blocked by SB203580, a specific inhibitor of mitogen-activated protein kinase p38, which also caused a dramatic destabilization of IFN-γ mRNA. The 3′ untranslated region (UTR) of IFN-γ mRNA conferred p38 responsiveness to a heterologous reporter mRNA. Therefore, the synergistic induction of IFN-γ by IL-12 and IL-18 in natural killer cells is mediated at least in part by p38-dependent and 3′ UTR-mediated stabilization of IFN-γ mRNA.</p
