Search results for "B-LYMPHOCYTE"
showing 10 items of 221 documents
Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron
2004
Abstract Iron(II) heme-mediated activation of the peroxide bond of artemisinins is thought to generate the radical oxygen species responsible for their antimalarial activity. We analyzed the role of ferrous iron in the cytotoxicity of artemisinins toward tumor cells. Iron(II)–glycine sulfate (Ferrosanol) and transferrin increased the cytotoxicity of free artesunate, artesunate microencapsulated in maltosyl-β-cyclodextrin, and artemisinin toward CCRF-CEM leukemia and U373 astrocytoma cells 1.5- to 10.3-fold compared with that of artemisinins applied without iron. Growth inhibition by artesunate and ferrous iron correlated with induction of apoptosis. Cell cycle perturbations by artesunate an…
The rheumatoid arthritis shared epitope increases cellular susceptibility to oxidative stress by antagonizing an adenosine-mediated anti-oxidative pa…
2006
We have recently demonstrated that the rheumatoid arthritis (RA) shared epitope (SE) acts as a ligand that triggers nitric oxide (NO) signaling in opposite cells. Given the known pro-oxidative effect of NO and the proposed role of oxidative stress in the pathogenesis of RA, this study explores whether SE-triggered signaling can increase cellular oxidative stress. cAMP levels, adenylyl cyclase activity, and protein kinase A activity were measured using commercial kits. Generation of reactive oxygen species (ROS) was quantified using the fluorochrome dichlorofluorescein diacetate. Oxidative DNA damage was quantified using the single-cell electrophoresis technique. Here, we report that cells e…
The matricellular protein SPARC supports follicular dendritic cell networking toward Th17 responses.
2011
Abstract Lymphnode swelling during immune responses is a transient, finely regulated tissue rearrangement, accomplished with the participation of the extracellular matrix. Here we show that murine and human reactive lymph nodes express SPARC in the germinal centres. Defective follicular dendritic cell networking in SPARC-deficient mice is accompanied by a severe delay in the arrangement of germinal centres and development of humoral autoimmunity, events that are linked to Th17 development. SPARC is required for the optimal and rapid differentiation of Th17 cells, accordingly we show delayed development of experimental autoimmune encephalomyelitis whose pathogenesis involves Th17. Not only h…
Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABA(A) receptor encephalitis
2021
Encephalitis associated with antibodies against the neuronal gamma-aminobutyric acid A receptor (GABA A -R) is a rare form of autoimmune encephalitis. The pathogenesis is still unknown but autoimmune mechanisms were surmised. Here we identified a strongly expanded B cell clone in the cerebrospinal fluid of a patient with GABA A -R encephalitis. We expressed the antibody produced by it and showed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry that it recognizes the GABA A -R. Patch-clamp recordings revealed that it tones down inhibitory synaptic transmission and causes increased excitability of hippocampal CA1 pyramidal neurons. Thus, the antibody likely contributed to…
Overexpression of Bcl-3 inhibits the development of marginal zone B cells.
2013
The transcription factor Bcl-3 functions as a proto-oncogene via regulation of cell proliferation and apoptosis. Bcl-3 is an atypical member of the IκB family and plays a central role in the immune response through interactions with the NF-κB subunits p50 and p52. To investigate the impact of Bcl-3 on B-cell maturation and regulation, we generated mice that overexpress Bcl-3 specifically in B cells. Interestingly, these mice lack marginal zone B cells and exhibit a significant reduction in the number of B-1 B cells. Further, B cells from these mice are impaired in their proliferative capacity. Our data demonstrate that the overexpression of the transcription factor Bcl-3 inhibits germinal c…
Interleukin 27 induces differentiation of neural C6-precursor cells into astrocytes.
2007
Interleukin 6 (IL6)-type cytokines are major regulators of inflammation and thereby contribute to the neuropathology and pathophysiology associated with inflammation of the central nervous system (CNS). Furthermore, astrocyte development which is a key process in the development of the CNS is also controlled by cytokines of the IL6-family. Interleukin 27 (IL27) is a recently identified member of this family and has been implicated in the inhibition of TH17 T-cell-responses. Here we show that IL27 and the HHV8 encoded viral IL6 (vIL6) induce C6 glioma cells to differentiate into an astrocyte-like state. Cytokine stimulation led to STAT-factor phosphorylation and consequently to protein expre…
Cytokines in the pathophysiology and treatment of chronic B-cell malignancies
1995
Chronic B-cell malignancies are characterized by accumulation of transformed B cells of low proliferative index in lymphatic and extralymphatic tissues. Cytokines do not appear to play a role in the primary step of transformation. However, proliferation as well as inhibition of apoptosis of malignant B cells can readily be explained by cytokine effects. Clinical trials of interferons (IFN) and interleukin-2 alone or in combination have been performed in patients with hairy cell leukemia (HCL), CLL, and low- and intermediate-grade non-Hodgkin's lymphoma. While IFN alpha became standard therapy of HCL, responses in other entities were variable, ranging from 0 to 70% in selected populations. C…
Pathogenesis of primary Sjögren's syndrome beyond B lymphocytes
2020
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder affecting exocrine glands of the body, prevalently lacrimal and salivary glands. The pSS pathogenesis has been thought to be B-cell-centric and several clinical trials have been carried out in order to clarify the therapeutic role of B-cell depletion in patients with pSS. Unfortunately, however, B-cell depletion with rituximab has failed in demonstrating any significant results in pSS patients. Besides the contribution of B cells in the pathogenesis of pSS, effector Tfh, Th17 and Th22 cells, follicular dendritic cells (DCs), innate cells (ICs) and several cytokines, chemokines and miRNA have been proved to participate to the …
Autoimmunity seen through the SEREX-scope.
2003
Autoantibodies can be detected in autoimmune diseases with a long prodromal phase and may serve as early indicators of disease activity. Autoantibody-based screening methods are therefore potent tools for the identification of target antigens. The SEREX method (serological identification of antigens by recombinant expression cloning) has been developed for the serological definition of immunogenic tumor antigens. Recent studies indicate that the SEREX approach may also be utilized for the analysis of complex immune responses involved in autoimmune diseases.
Invariant NKT cells are expanded in peripheral blood but are undetectable in salivary glands of patients with primary Sjögren's syndrome
2016
OBJECTIVES: Invariant NKT (iNKT) cells play a role in regulating the function of autoreactive B cells before their entry into germinal centres. Absence and/or reduction of iNKT cells have been demonstrated in patients with systemic lupus erythematosus (SLE) together with an increase of autoreactive B cell activity. Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease in which lymphocyte infiltration and organisation in lymphoid structures of inflamed salivary glands occurs. The aim of the study was to investigate the percentage and function of iNKT in the salivary glands and peripheral blood of patients with pSS. METHODS: Minor salivary gland biopsies were obtained from patient…