Search results for "Cell activation"
showing 10 items of 43 documents
The influence of leflunomide on cell cycle, IL-2-receptor (IL-2-R) and its gene expression
1994
Leflunomide is a novel immunomodulatory drug shown to be very effective in animal models of autoimmune diseases and transplantation rejection, as well as in human rheumatoid arthritis. Leflunomide's main metabolite, A77 1726, has been shown to be reversibly antiproliferativein vitro. Pursuing this, we performed cell cycle analysis by flow cytometry of a B-cell lymphoma line and found that at concentrations >2.5 μM cells accumulated in the early S-phase. In order to determine A77 1726's effects on cell activation, human peripheral blood lymphocytes (PBL) were cultured in the presence of PHA or OKT 3 antibody. Flow cytometric evaluation of IL-2 and transferrin receptor expression exhibited a …
Retinal neurodegenerative changes in the adult insulin receptor substrate-2 deficient mouse.
2014
Abstract Insulin receptor substrate-2 (Irs2) mediates peripheral insulin action and is essential for retinal health. Previous investigations have reported severe photoreceptor degeneration and abnormal visual function in Irs2-deficient mice. However, molecular changes in the Irs2 − / − mouse retina have not been described. In this study, we examined retinal degenerative changes in neuronal and glial cells of adult (9- and 12-week old) Irs2 − / − mice by immunohistochemistry. 9-week old Irs2 − / − mice showed significant thinning of outer retinal layers, concomitant to Muller and microglial cell activation. Photoreceptor cells displayed different signs of degeneration, such as outer/inner…
Arginine deficiency leads to impaired cofilin dephosphorylation in activated human T lymphocytes
2012
The amino acid arginine is fundamentally involved in the regulation of the immune response during infection, inflammatory diseases and tumor growth. Arginine deficiency (e.g. due to the myeloid cell enzyme arginase) inhibits proliferation and effector functions of activated T lymphocytes. Here, we studied intracellular mechanisms mediating this suppression of human T lymphocytes. Our proteomic analysis revealed an impaired dephosphorylation of the actin-binding protein cofilin upon T-cell activation in the absence of arginine. We show that this correlates with alteration of actin polymerization and impaired accumulation of CD2 and CD3 in the evolving immunological synapse in T cell-antigen …
The role of NF-AT transcription factors in T cell activation and differentiation11We dedicate this review to Prof. Dr. Rigomar Rieger (Gatersleben), …
2000
AbstractThe family of genuine NF-AT transcription factors consists of four members (NF-AT1 [or NF-ATp], NF-AT2 [or NF-ATc], NF-AT3 and NF-AT4 [or NF-ATx]) which are characterized by a highly conserved DNA binding domain (is designated as Rel similarity domain) and a calcineurin binding domain. The binding of the Ca2+-dependent phosphatase calcineurin to this region controls the nuclear import and exit of NF-ATs. This review deals (1) with the structure of NF-AT proteins, (2) the DNA binding of NF-AT factors and their interaction with AP-1, (3) NF-AT target genes, (4) signalling pathways leading to NF-AT activation: the role of protein kinases and calcineurin, (5) the nuclear entry and exit …
Idelalisib Impairs TREM-1 and TLR Mediated Neutrophil Activation
2016
Abstract Introduction: Polymorphonuclear neutrophils (PMN) play an essential role in innate inflammatory processes. Their functions are strictly regulated and many activating / inhibiting mechanisms along with their pathways are only incompletely understood. Besides toll-like receptors (TLR) and NOD-like receptors (NLR), triggering receptor expressed on myeloid cells (TREM)-1 is implicated in innate immune activation of these cells and plays a role in infectious as well as non-infectious conditions. Activation of TREM-1 results in release of pro-inflammatory chemokines and cytokines, increased surface expression of cell activation markers and degranulation. In TREM-1 downstream pathways and…
Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation
2020
AbstractThe pathophysiology of endometriosis (EM) is an excellent example of immune dysfunction, reminiscent of tumor microenvironment as well. Here, we report that an interplay between C3 and mast cells (MCs) is involved in the pathogenesis of ectopic EM. C3 is at the epicenter of the regulatory feed forward loop, amplifying the inflammatory microenvironment, in which the MCs are protagonists. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse, into the peritoneum of the recipient mice. The wild type mice showed greater amount of…
Naturally occurring short splice variant of CYLD positively regulates dendritic cell function
2009
Abstract Deubiquitination of NF-κB members by CYLD is crucial in controlling the magnitude and nature of cell activation. The role of the naturally occurring CYLD splice variant in dendritic cell (DC) function was analyzed using CYLDex7/8 mice, which lack the full-length CYLD (flCYLD) transcript and overexpress the short splice variant (sCYLD). Bone marrow–derived DCs from CYLDex7/8 mice display a hyperactive phenotype in vitro and in vivo and have a defect in establishing tolerance with the use of DEC-205–mediated antigen targeting to resting DCs. The combination of sCYLD overexpression and lack of flCYLD in CYLDex7/8 DCs leads to enhanced NF-κB activity accompanied by an increased nuclear…
Generation of an Eosinophilotactic Factor from Human PMNs by Various Mechanisms of Cell Activation
1979
It is well established that an increase in the number of eosinophils both in tissue and in the circulation is a feature of many clinical conditions based on delayed (1,2) and immediate type hypersensitivity reactions (3,4). Since eosinophils have been recognised to exert specific killer function on parasites (5) and to be prominent participants at sites of inflammation, the mechanisms of their chemo-attraction are of major importance. In immediate type hypersensitivity reactions, eosinophils have been demonstrated to counteract the mediators of inflammation such as histamine (6), the SRS-A (7) and the platelet aggregating factor (8).
IL-2 Expression in Activated Human Memory FOXP3(+) Cells Critically Depends on the Cellular Levels of FOXP3 as Well as of Four Transcription Factors …
2012
The human CD4(+)FOXP3(+) T cell population is heterogeneous and consists of various subpopulations which remain poorly defined. Anergy and suppression are two main functional characteristics of FOXP3(+)Treg cells. We used the anergic behavior of FOXP3(+)Treg cells for a better discrimination and characterization of such subpopulations. We compared IL-2-expressing with IL-2-non-expressing cells within the memory FOXP3(+) T cell population. In contrast to IL-2-non-expressing FOXP3(+) cells, IL-2-expressing FOXP3(+) cells exhibit intermediate characteristics of Treg and Th cells concerning the Treg cell markers CD25, GITR, and Helios. Besides lower levels of FOXP3, they also have higher levels…
Leukotriene B4-loaded microspheres: a new therapeutic strategy to modulate cell activation
2008
AbstractBackgroundLeukotriene B4(LTB4) is a potent inflammatory mediator that also stimulates the immune response. In addition, it promotes polymorphonuclear leukocyte phagocytosis, chemotaxis, chemokinesis and modulates cytokines release. Regarding chemical instability of the leukotriene molecule, in the present study we assessed the immunomodulatory activities conferred by LTB4released from microspheres (MS). A previous oil-in-water emulsion solvent extraction-evaporation method was chosen to prepare LTB4-loaded MS.ResultsIn the mice cremasteric microcirculation, intraescrotal injection of 0.1 ml of LTB4-loaded MS provoked significant increases in leukocyte rolling flux, adhesion and emig…