Tag Archives: U0126-EtOH

Introduction Intercellular adhesion molecule-1 (ICAM-1) is definitely involved in migration and

Introduction Intercellular adhesion molecule-1 (ICAM-1) is definitely involved in migration and co-stimulation of T and B cells. not show any change in U0126-EtOH focus scores, but immunohistochemical staining showed an increase in the overall number of CD4+ and CD8+ T cells. Moreover, early treated mice showed decreased IgM within the SGs, whereas late treated mice had increased IgM levels, and on average U0126-EtOH higher IgG and IgA. Conclusions Blocking the ICAM-1/LFA-1 interaction with sICAM-1/Fc may result in worsening of a SS like phenotype when infiltrates have already formed within the SG. As a treatment for human SS, caution should be taken targeting the ICAM-1 axis since U0126-EtOH most patients are diagnosed when inflammation is clearly present within the SG. Introduction Intercellular adhesion molecule-1 (ICAM-1) binds to lymphocyte function-associated antigen-1 (LFA-1) and macrophage 1 antigen (Mac-1) on immune cells, and is involved in adhesion and migration of leucocytes in an inflammatory environment. ICAM-1 also plays an important role in the co-stimulatory pathway involved in T cell activation and clonal expansion [1], and T cell dependent B cell activation [2]. ICAM-1 is upregulated in endothelial cells, lymphocytes, fibroblasts, and ductal epithelium of salivary glands (SG) from Sj?gren’s syndrome (SS) patients [3], [4], [5], [6]. SS is a systemic autoimmune disorder affecting secretory tissue, including the lachrymal and salivary glands, resulting in keratoconjunctivitis sicca and xerostomia. One of the pathological hallmarks of the disease is the focal infiltration of mononuclear cells into these secretory glands. Currently, there is no effective treatment for SS. Since ICAM-1 is consistently found to be upregulated in SS, it has been suggested that targeting ICAM-1 and the interaction with its ligands may favorably affect the condition result [7], [8]. In earlier studies, obstructing ICAM-1 discussion by systemic administration of sICAM-1, offers shown to be a highly effective therapy for autoimmune diabetes in the Non Obese Diabetic (NOD) mouse. Intraperitoneal (ip) shot with sICAM-1 prior to the medical starting point of disease in NOD mice, led to reduced monocytic infiltration in to the pancreas, decreased Th1 cytokines levels and a lower diabetes incidence [9]. Another study showed that treatment of NOD mice with sICAM-1 after the onset of diabetes resulted in long-term remission of diabetes in >50% of treated mice. Interestingly, remission was not accompanied by decreased diabetogenic T cells and did not result in overall immunosuppression, suggesting induction of tolerance by sICAM-1 [10]. Independent of diabetes [11], the NOD mice also spontaneously develop a complex of features that resembles SS in humans [11]. These mice spontaneously develop SG focal infiltrates, mainly consisting of B and T cells, and within the inflamed SG, membrane bound endothelial and epithelial ICAM-1 and LFA-1 are upregulated [12]. These characteristics make the NOD mouse a reasonable model to study the potential therapeutic effect of ICAM-1 interference on the development of SS. Since ICAM-1 plays a role in the migration of immune cells into tissue, we tested the effect of sICAM-1 overexpression and secretion by ductal cells in SG of NOD mice, before (early treatment) and after (late treatment) the influx of inflammatory cells, to see whether we can intervene with the formation of U0126-EtOH the first focal infiltrates. The ductal cells are thought to play a crucial role in the pathogenesis of SS [13] since focal U0126-EtOH infiltrates in SS are mainly found surrounding the ductal epithelial cells. Moreover, ductal cells produce high levels of pro-inflammatory cytokines and can act as nonprofessional antigen presenting cells [14], making these cells an attractive target. In Ccna2 this study, we investigated whether sustained expression of sICAM-1 by ductal epithelial cells via local gene.