Research Interests: Pathogenesis, Flow Cytometry, Biology, Medicine, Hepatitis C, and 15 moreMultidisciplinary, Signal Transduction, Humans, Female, Male, Hepatitis C Virus, Middle Aged, Human Genome, Adult, European Continental Ancestry Group, Reference Values, Gene expression profiling, Interferon Alpha, Hepacivirus, and gene amplification
Research Interests: Engineering, Computer Science, Machine Learning, Data Mining, Computational Biology, and 15 moreGene expression, Bayesian Networks, Feature Selection, Genetic Association Studies, KEGG, Bayesian Network, Rank Aggregation, Reference model, Bayesian model, Genetic Association, Bayesian Probability, Cascade, Feature Subset Selection, Usability Evaluation Method, and Ranking algorithm
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Research Interests: Engineering, Computer Science, Machine Learning, Data Mining, Computational Biology, and 15 moreGene expression, Bayesian Networks, Feature Selection, Genetic Association Studies, KEGG, Bayesian Network, Rank Aggregation, Reference model, Bayesian model, Genetic Association, Bayesian Probability, Cascade, Feature Subset Selection, Usability Evaluation Method, and Ranking algorithm
The transcription factor junB belongs to the jun family of protooncogenes. The appearence of junB mRNA in hepatic cells is an extremely early and sensitive marker of the action of proinflammatory cytokines including interleukin-6. In this... more
The transcription factor junB belongs to the jun family of protooncogenes. The appearence of junB mRNA in hepatic cells is an extremely early and sensitive marker of the action of proinflammatory cytokines including interleukin-6. In this study, a competitive reverse transcription (RT)-PCR assay has been developed that is suitable for the quantitative determination of junB mRNA expression. This nonisotopic assay compared to other methods (e.g., Northern blot) is a fast and convenient way to determine the expression of the junB gene and thus the immediate concentration- and time-dependent action of interleukin-6. Because interleukin-6 and interleukin-6-type cytokines play a highly important regulatory role in various pathophysiologically important processes, such as hepatic acute-phase reaction, the quantitative assay of junB mRNA completes the scale of laboratory approaches in inflammation and among other pathological conditions.
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Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding of the complex interactions among their respective disease pathways preclude successful treatment and prevention. The placenta has a key role... more
Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding of the complex interactions among their respective disease pathways preclude successful treatment and prevention. The placenta has a key role in the pathogenesis of the terminal pathway characterized by exaggerated maternal systemic inflammation, generalized endothelial damage, hypertension, and proteinuria. This of preeclampsia may be triggered by distinct underlying mechanisms that occur at early stages of pregnancy and induce different phenotypes. To gain insights into these molecular pathways, we employed a systems biology approach and integrated different "omics," clinical, placental, and functional data from patients with distinct phenotypes of preeclampsia. First trimester maternal blood proteomics uncovered an altered abundance of proteins of the renin-angiotensin and immune systems, complement, and coagulation cascades in patients with term or preterm preeclampsia. More...
Research Interests: Systems Biology, Biomarkers, Biology, Proteomics, Medicine, and 8 morePregnancy, Humans, Placenta, Preeclampsia, Female, Adult, Trophoblast, and Pre Eclampsia
Research Interests: Endocrinology, Medicine, Insulin Resistance, Humans, Internal Medicine, and 15 moreHungary, Female, Male, Leptin, Cohort, Adipokines, Aged, Middle Aged, Adiponectin, Adult, Cross Sectional Studies, Case Control Studies, Cohort Studies, Medical and Health Sciences, and Genetic predisposition to disease
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Incubation of purified human beta 2-microglobulin (B2-m) with tissue transglutaminase (Tgase) resulted in the formation of high molecular weight polymers revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In the... more
Incubation of purified human beta 2-microglobulin (B2-m) with tissue transglutaminase (Tgase) resulted in the formation of high molecular weight polymers revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In the presence of 30 mM [14C]methylamine, the polymer formation was prevented, but incorporation of methylamine into beta 2-m (equal to 1 methylamine per 1 molecule) could be observed. From the sheddings of peripheral blood mononuclear cells occurring in the presence of Tgase, it is apparent that anti-beta 2-m immunoadsorbent removed, in addition to human leukocyte antigen (HLA) and beta 2-m, some other proteins. The enzyme could incorporate [14C]methylamine into beta 2-m of the shedding cells. On addition of rabbit anti-human beta 2-m antibody, followed by fluoresceine-labeled goat anti-rabbit IgG antibody to human mononuclear blood cells, the otherwise homogeneous distribution of fluorescence turned into spots and patches on cells previously incubated with Tg...
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Limited responsiveness to IFN-α in hepatitis C virus (HCV)-infected African-Americans compared to European Americans (AAs vs. EAs) hinders the management of HCV. Here, we studied healthy non-HCV-infected AA and EA subjects to test whether... more
Limited responsiveness to IFN-α in hepatitis C virus (HCV)-infected African-Americans compared to European Americans (AAs vs. EAs) hinders the management of HCV. Here, we studied healthy non-HCV-infected AA and EA subjects to test whether immune cell response to IFN-α is determined directly by race. We compared baseline and IFN-α-induced signal transducer and activator of transcription (STAT)-1, STAT-2, STAT-3, STAT-4, and STAT-5 protein and phosphorylation levels in purified T cells, global transcription, and a genomewide single-nucleotide polymorphism (SNP) profile of healthy AA and EA blood donors. In contrast to HCV-infected individuals, healthy AAs displayed no evidence of reduced STAT activation or IFN-α-stimulated gene expression compared to EAs. Although >200 genes reacted to IFN-α treatment, race had no impact on any of them. The only gene differentially expressed by the two races (NUDT3, P < 10 −7 ) was not affected by IFN-α and bears no known relationship to IFN-α s...
Research Interests: Pathogenesis, Flow Cytometry, Biology, Medicine, Hepatitis C, and 15 moreMultidisciplinary, Signal Transduction, Humans, Female, Male, Hepatitis C Virus, Middle Aged, Human Genome, Adult, European Continental Ancestry Group, Reference Values, Gene expression profiling, Interferon Alpha, Hepacivirus, and gene amplification
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C5-deficient mice differed from C5-sufficient mice both quantitatively and qualitatively in C5 protein, C5 mRNA, and the C5 gene. C5-deficient protein was present as decreased amounts of an unprocessed, single-chain precursor.... more
C5-deficient mice differed from C5-sufficient mice both quantitatively and qualitatively in C5 protein, C5 mRNA, and the C5 gene. C5-deficient protein was present as decreased amounts of an unprocessed, single-chain precursor. C5-deficient mRNA was decreased in amount and present in two forms, the smaller of which was the same as the single form in normal cells. Nuclei from both normal and deficient cells contained the larger form of C5 mRNA, and C5-deficient DNA demonstrated differences from the normal pattern on Southern analysis for two restriction enzymes. These data suggest that the primary transcript of the C5-deficient gene is abnormal, retarding the processing of the C5 mRNA, and that the C5-deficient mRNA codes for an abnormal protein.
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The discovery of the biological relevance of non-coding RNA molecules represents one of the most significant advances in contemporary molecular biology. It has turned out that a major fraction of the non-coding part of the genome is... more
The discovery of the biological relevance of non-coding RNA molecules represents one of the most significant advances in contemporary molecular biology. It has turned out that a major fraction of the non-coding part of the genome is transcribed. Beside small RNAs (including microRNAs) more and more data are disclosed concerning long non-coding RNAs of 200 nucleotides to 100 kb length that are implicated in the regulation of several basic molecular processes (cell proliferation, chromatin functioning, microRNA-mediated effects, etc.). Some of these long non-coding RNAs have been associated with human tumours, including H19, HOTAIR, MALAT1, etc., the different expression of which has been noted in various neoplasms relative to healthy tissues. Long non-coding RNAs may represent novel markers of molecular diagnostics and they might even turn out to be targets of therapeutic intervention. Orv. Hetil., 2012, 153, 1494–1501.
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Research Interests: Library Science, Immunology, Gastroenterology, Biology, Immunohistochemistry, and 15 moreHelicobacter pylori, Medicine, Internal Medicine, Citation, Clinical Sciences, Gut, Asymptomatic, Gastritis, Neurosciences, Gastrin, Cell Growth, Gerbil, Gastric mucosa, Clinical Gastroenterology, and Paediatrics and reproductive medicine
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The effects of linearly polarized light (LPL) and diffuse light (DL) on the in vitro interleukin‐6 (IL‐6) production in a human B lymphoma cell line (BMNH) and peripheral monocytes of healthy volunteers were compared. Our data show that... more
The effects of linearly polarized light (LPL) and diffuse light (DL) on the in vitro interleukin‐6 (IL‐6) production in a human B lymphoma cell line (BMNH) and peripheral monocytes of healthy volunteers were compared. Our data show that there was a significant increase of IL‐6 and IgM production in BMNH after exposure to LPL. The increase in IgM secretion was a consequence of its autocrine regulation by IL‐6, since in the presence of anti‐IL‐6 and anti‐IL‐6 receptor antibodies the LPL‐induced IgM secretion was abolished. In contrast to the stimulatory effect on B cells, exposure of human mononuclear phagocytes to LPL markedly reduced the production of IL‐6 induced by subsequent stimulation of cells with bacterial endotoxin (LPS). The inhibition as most pronounced when suboptimal doses of LPS were applied. Under identical experimental conditions, DL had no effect on the IL‐6 and IgM production of either B cells or monocytes.
Research Interests: Biology, Wound Healing, Cytokines, Cell Biology, Medicine, and 15 moreCell line, In Vitro, Humans, Light, Monocytes, Diffuse Large B-Cell Lymphoma, Stimulation, Polarized Light Microscopy, Secretion, Biochemistry and cell biology, Interleukin, immunoglobulin M, Diffuse large B cell lymphoma, Monocyte, and B cell
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Basophil numbers are typically elevated in chronic myeloid leukemia (CML) and increase during disease progression. Histamine is an essential mediator and marker of basophils and is highly up-regulated in CML. We examined the biochemical... more
Basophil numbers are typically elevated in chronic myeloid leukemia (CML) and increase during disease progression. Histamine is an essential mediator and marker of basophils and is highly up-regulated in CML. We examined the biochemical basis of histamine synthesis in CML cells. The CML-specific oncoprotein BCR/ABL was found to promote expression of histidine decarboxylase (HDC) and synthesis of histamine in Ba/F3 cells. Moreover, the BCR/ABL tyrosine kinase inhibitors imatinib (STI571) and nilotinib (AMN107) decreased histamine levels and HDC mRNA expression in BCR/ABL-transformed Ba/F3 cells, in the CML-derived basophil cell line KU812, and in primary CML cells. Synthesis of histamine was found to be restricted to the basophil compartment of the CML clone and to depend on signaling through the PI3-kinase pathway. CML cells also expressed histamine receptors (HRs), including HR-1, HR-2, HR-4, and histamine-binding CYP450 isoenzymes which also serve as targets of HR antagonists. The...
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Research Interests: Immunology, Kidney diseases, Rheumatoid Arthritis, Medicine, Humans, and 12 moreSystemic Lupus Erythematosus, Statistical Significance, Immunoglobulin E, Arthritis, Clinical Sciences, Immune system, Polyethylene Glycol, Antibody, Public health systems and services research, Healthy Subjects, Immune Complex, and Polyethylene Glycols
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Research Interests: Engineering, Cancer, Flow Cytometry, Biology, France, and 15 moreGene expression, Disease susceptibility, Cats, Biological Sciences, Association study, Animal Genetics, Female, Animals, Drug Resistance, Gene, Clinical Sciences, Clopidogrel, Base Sequence, Amino Acid Substitution Rates, and Citrullus lanatus
Research Interests: Immunology, Rheumatoid Arthritis, Medicine, Humans, Female, and 15 moreMale, Immunoglobulin E, Clinical Sciences, Aged, Middle Aged, Immune system, Polyethylene Glycol, Antibody, Chemical Precipitation, Public health systems and services research, Immune Complex, Polyethylene Glycols, Autoantibodies, Total protein, and Felty Syndrome
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Research Interests: Humanities and ISBN
Allergia genomika: ismert és teljes genomszűréssel kiemelt asthmára hajlamosító gének vizsgálata emberben és transzgenikus állatmodellen valamint európai összevetésre alkalmas hazai asthma biobank létrehozása = Allergy genomics: Studies on known and other asthma susceptibility genes found by whol...more
Cell derived extracellular vesicles are submicron structures surrounded by phospholipid bilayer and released by both prokaryotic and eukaryotic cells. The sizes of these vesicles roughly fall into the size ranges of microbes, and they... more
Cell derived extracellular vesicles are submicron structures surrounded by phospholipid bilayer and released by both prokaryotic and eukaryotic cells. The sizes of these vesicles roughly fall into the size ranges of microbes, and they represent efficient delivery platforms targeting complex molecular information to professional antigen presenting cells. Critical roles of these naturally formulated units of information have been described in many physiological and pathological processes. Extracellular vesicles are not only potential biomarkers and possible pathogenic factors in numerous diseases, but they are also considered as emerging therapeutic targets and therapeutic vehicles. Strikingly, current drug delivery systems, designed to convey therapeutic proteins and peptides (such as liposomes), show many similarities to extracellular vesicles. Here we review some aspects of therapeutic implementation of natural, cell-derived extracellular vesicles in human diseases. Exploration of ...
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Posttranslational modifications are chemical changes to proteins that take place after synthesis. One such modification, peptidylarginine to peptidylcitrulline conversion, catalysed by peptidylarginine deiminases, has recently received... more
Posttranslational modifications are chemical changes to proteins that take place after synthesis. One such modification, peptidylarginine to peptidylcitrulline conversion, catalysed by peptidylarginine deiminases, has recently received significant interest in biomedicine. Introduction of citrulline dramatically changes the structure and function of proteins. It has been implicated in several physiological and pathological processes. Physiological processes include epithelial terminal differentiation, gene expression regulation, and apoptosis. Rheumatoid arthritis, multiple sclerosis, and Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease are examples of human diseases where protein citrullination involvement has been demonstrated. In this review, we discuss our current understanding on the importance of protein deimination in these processes. We describe the enzymes catalyzing the reaction, as well as their known protein substrates. We review the citrullinated peptide epitopes that are proposed as disease markers, specifically recognized in certain human autoimmune disorders. The potential autopathogenic role of citrullinated epitopes is also discussed.
Research Interests: Multiple sclerosis, Biology, Rheumatoid Arthritis, Cell Biology, Medicine, and 14 moreProtein Structure and Function, Humans, Autoimmune diseases, The, Proteins, Enzyme, Biological markers, Human Disease, Citrulline, Glycosyl Hydrolases, Differential Gene Expression, Biochemistry and cell biology, epitope, and Citrullination
Targeted disruption of the histidine decarboxylase gene (HDC −/− ), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired... more
Targeted disruption of the histidine decarboxylase gene (HDC −/− ), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC −/− mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC −/− mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1α-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Seru...
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Histamine is synthesized in cells by histidine decarboxylase (HDC). HDC-deficient knockout (KO) mice lack functional HDC and histamine in the tissues. In the present study we used this in vivo model for studying the role of HDC deficiency... more
Histamine is synthesized in cells by histidine decarboxylase (HDC). HDC-deficient knockout (KO) mice lack functional HDC and histamine in the tissues. In the present study we used this in vivo model for studying the role of HDC deficiency in the regulation of male steroid hormone metabolism. In agreement with earlier studies showing the lack of effects of central histamine on the basal secretion of gonadotrope hormones, we found no difference with in situ hybridization in the expression of GnRH in the hypothalamus of wild type and KO mice. The tissue concentrations of testosterone and several androgenic steroids were significantly elevated in the testes but not in the adrenal glands of HDC-KO mice. In contrast, serum estradiol levels failed to show a significant difference between the two groups. The weight of the testes was significantly smaller in both 7-day-old and adult KO mice. The ultrastructure of the adult testis indicated elevated steroid synthesis with more tightly coiled ...
Research Interests: Endocrinology, Electron Microscopy, Biology, Scanning Electron Microscopy, Medicine, and 15 moreAnimal Production, In Situ Hybridization, Fetal development, Histamine, Internal Medicine, Mice, Animals, Male, Androgens, Clinical Sciences, Analysis of Variance, Adrenal Gland, Leydig cells, Adrenal glands, and Gene knockout
Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC‐deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked... more
Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC‐deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked histamine‐synthesizing activity from histidine. These HDC‐deficient mice are viable and fertile but exhibit a decrease in the numbers of mast cells while the remaining mast cells show an altered morphology and reduced granular content. The amounts of mast cell granular proteases were tremendously reduced. The HDC‐deficient mice provide a unique and promising model for studying the role of histamine in a broad range of normal and disease processes.
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Research Interests: Humanities and ISBN
Extracellular vesicles (EVs) are membrane-enclosed subcellular structures released by all cell types. EVs have important roles in both cellular homeostasis and intercellular communication. Recent progress in the field revealed substantial... more
Extracellular vesicles (EVs) are membrane-enclosed subcellular structures released by all cell types. EVs have important roles in both cellular homeostasis and intercellular communication. Recent progress in the field revealed substantial heterogeneity of EVs even within the size-based EV categories. Here we addressed the question whether the exportin-1 (XPO1)-mediated nuclear export of RNAs contributed to the EV heterogeneity. Size-based populations were separated from the conditioned media of three cell lines (U937, THP-1 and 5/4E8) in steady-state condition. The effects of activation and leptomycin B treatment (to inhibit the XPO1-mediated nuclear export of RNAs) were also tested in the case of the two monocytic cell lines. Agilent Pico and Small chips were used to characterize RNAs, fragment analysis was performed, and EV-associated miRNAs were tested by Taqman assays. As expected, we found the highest small RNA/total RNA ratio and the lowest rRNA/total RNA proportion in small E...
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Orsolya Lautner-Csorba (cs.orsi@gmail.com) András Gézsi (gezsi.andras@gmail.com) Ágnes F Semsei (f.semseia@gmail.com) Dániel J Edélyi (erddan@gmail.com) Péter Antal (antal@mit.bme.hu) Géza Schermann (schermann.geza@gmail.com) Nóra... more
Orsolya Lautner-Csorba (cs.orsi@gmail.com) András Gézsi (gezsi.andras@gmail.com) Ágnes F Semsei (f.semseia@gmail.com) Dániel J Edélyi (erddan@gmail.com) Péter Antal (antal@mit.bme.hu) Géza Schermann (schermann.geza@gmail.com) Nóra Kutszegi (norakutszegi@hotmail.com) Katalin Csordás (csordaskatalin@gmail.com) Márta Hegyi (marta.hegyi@gmail.com) Gábor Kovács (kovi@gyer2.sote.hu) András Falus (afalus@gmail.com) Csaba Szalai (genomika.cs@gmail.com)
Hypersensitivity reactions are the most frequent dose-limiting adverse reactions to Escherichia coli-derived asparaginase in pediatric acute lymphoblastic leukemia patients. The aim of the present study was to identify associations... more
Hypersensitivity reactions are the most frequent dose-limiting adverse reactions to Escherichia coli-derived asparaginase in pediatric acute lymphoblastic leukemia patients. The aim of the present study was to identify associations between sequence-based Human Leukocyte Antigen Class II region alleles and asparaginase hypersensitivity in a Hungarian acute lymphoblastic leukemia population. Four-digit typing of HLA-DRB1 and HLA-DQB1 loci was performed in 359 pediatric acute lymphoblastic leukemia patients by using next-generation sequencing method. Based on genotypic data of the two loci, haplotype reconstruction was carried out. In order to investigate the possible role of the HLA-DQ complex, the HLA-DQA1 alleles were also inferred. Multivariate logistic regression analysis and a Bayesian network-based approach were applied to identify relevant genetic risk factors of asparaginase hypersensitivity. Patients with HLA-DRB1*07:01 and HLA-DQB1*02:02 alleles had significantly higher risk...
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Research Interests: Biology, Membrane Proteins, Dermatology, Mast Cells, Cancer Research, and 15 moreMedicine, Gene expression, Cell line, Humans, Melanoma, Epidermis, Clinical Sciences, Reproducibility of Results, Melanocytes, INVESTIGATIVE, Ligands, Immunoglobulin, Skin Neoplasms, Transforming Growth Factor, and Galectins
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Decreased expression of the TCR ζ-chain has been reported in several autoimmune, inflammatory, and malignant diseases, suggesting that ζ-chain downregulation is common at sites of chronic inflammation. Although ζ-chain is critically... more
Decreased expression of the TCR ζ-chain has been reported in several autoimmune, inflammatory, and malignant diseases, suggesting that ζ-chain downregulation is common at sites of chronic inflammation. Although ζ-chain is critically important in T lymphocyte activation, the mechanism of the decreased ζ-chain expression is less clear. Src-like adaptor protein (SLAP) is a master regulator of T cell activation; previous data have reported that SLAP regulates immunoreceptor signaling. We have examined the mechanism and the functional consequences of CD3 ζ-chain downregulation. TNF treatment of human T lymphocytes (15–40 ng/ml) selectively downregulates CD3 ζ-chain expression in a dose-dependent manner (p < 0.05) and decreases activation-induced IL-2 expression (p < 0.01). Although blocking of the lysosomal compartment fails to restore TNF-induced CD3 ζ-chain downregulation, inhibition of the proteasome prevented the effect of TNF. Both SLAP expression and the colocalization of SLA...