scholarly journals Induction of high-affinity interleukin 1 receptor on human peripheral blood lymphocytes by glucocorticoid hormones.

1988 ◽  
Vol 167 (3) ◽  
pp. 924-936 ◽  
Author(s):  
T Akahoshi ◽  
J J Oppenheim ◽  
K Matsushima
Keyword(s):  
Human Peripheral Blood ◽  
Specific Binding ◽  
Interleukin 1 ◽  
Major Change ◽  
Peripheral Blood Lymphocytes ◽  
Dermal Fibroblasts ◽  
Maximal Effect ◽  
Vitro Effect

The in vitro effect of glucocorticoids (GCs) on IL-1-R expression of human PBMCs was investigated. Both physiological and pharmacological concentration ranges of GC increased the specific binding of 125I-labeled human rIL-1 alpha to PBMCs. This enhancement was specific for GC, since other steroid hormones, such as progesterone, 17 beta-estradiol, and testosterone failed to elevate the binding of 125I-IL-1 alpha to PBMCs. The effect was time dependent with maximal effect occurring 6 h after treatment and dose dependent with half-maximal effect elicited by 100 nM prednisolone. Scatchard plot analysis indicated that 125I-IL-1 alpha binding increased from approximately 100 IL-1-R per cell to 2 X 10(3) receptors per cell without a major change in affinity (Kd = 2.6 X 10(-10) M). The subpopulation of PBMCs induced by GC to express higher levels of IL-1-R consisted predominantly of B lymphocytes, but not T lymphocytes, large granular lymphocytes, or monocytes. GCs also induced the expression of IL-1-R on some other cell types, including normal human dermal fibroblasts and the human large granular lymphocyte cell line YT. Since cycloheximide and actinomycin D inhibited the induction of IL-1-R by GC, synthesis of both new RNA and protein seems to be required for IL-1-R induction. This study presents the first evidence of upregulation of the receptors for IL-1 by GC, and may account for the reported enhancement of in vitro and in vivo humoral immune responses by GCs.

scholarly journals Expression of pro-inflammatory markers by human dermal fibroblasts in a three-dimensional culture model is mediated by an autocrine interleukin-1 loop

2004 ◽  
Vol 379 (2) ◽  
pp. 351-358 ◽  
Author(s):  
Daniela KESSLER-BECKER ◽  
Thomas KRIEG ◽  
Beate ECKES
Keyword(s):  
Keratinocyte Growth Factor ◽  
Interleukin 1 ◽  
Three Dimensional ◽  
Dermal Fibroblasts ◽  
Human Dermal Fibroblasts ◽  
Inflammatory Processes ◽  
Cox 2 ◽  
Extracellular Matrix Interactions

In vivo, fibroblasts reside in connective tissues, with which they communicate in a reciprocal way. Such cell–extracellular matrix interactions can be studied in vitro by seeding fibroblasts in collagen lattices. Depending upon the mechanical properties of the system, fibroblasts are activated to assume defined phenotypes. In the present study, we examined a transcriptional profile of primary human dermal fibroblasts cultured in a relaxed collagen environment and found relative induction (>2-fold) of 393 out of approx. 7100 transcripts when compared with the same system under mechanical tension. Despite down-regulated proliferation and matrix synthesis, cells did not become generally quiescent, since they induced transcription of numerous other genes including matrix metalloproteinases (MMPs) and growth factors/cytokines. Of particular interest was the induction of gene transcripts encoding pro-inflammatory mediators, e.g. cyclo-oxygenase-2 (COX-2), and interleukins (ILs)-1 and -6. These are apparently regulated in a hierarchical fashion, since the addition of IL-1 receptor antagonist prevented induction of COX-2, IL-1 and IL-6, but not that of MMP-1 or keratinocyte growth factor (KGF). Our results suggest strongly that skin fibroblasts are versatile cells, which adapt to their extracellular environment by displaying specific phenotypes. One such phenotype, induced by a mechanically relaxed collagen environment, is the ‘pro-inflammatory’ fibroblast. We propose that fibroblasts that are embedded in a matrix environment can actively participate in the regulation of inflammatory processes.

scholarly journals The chemotactic attraction of human fibroblasts to a lymphocyte-derived factor.

1976 ◽  
Vol 144 (5) ◽  
pp. 1188-1203 ◽  
Author(s):  
A E Postlethwaite ◽  
R Snyderman ◽  
A H Kang
Keyword(s):  
Connective Tissue ◽  
Peripheral Blood ◽  
Human Fibroblasts ◽  
Peripheral Blood Lymphocytes ◽  
Dermal Fibroblasts ◽  
Chemotactic Factor ◽  
Human Dermal Fibroblasts ◽  
Heat Stable

A quantitative assay that measures fibroblast chemotaxis in vitro is described. Application of this technique has revealed that peripheral blood lymphocytes stimulated by antigen or mitogen in vitro produce a factor that is chemotactic for human dermal fibroblasts. This lymphocyte-derived chemotactic factor for fibroblasts (LDCF-F) is different from the lymphokine that is chemotactic for monocytes or macrophages. Macrophages are required for the generation of LDCF-F by T lymphocytes stimulated by phytohemagglutinin. The fibroblast chemotactic factor is heat stable (56 degrees C for 30 min), trypsin sensitive, and neuraminidase resistant. LDCF-F could function to attact connective tissue fibroblasts to sites at which cell-mediated immune reactions are occurring in vivo.

scholarly journals Assessment of biosafety and toxicity of hydrophilic gel for implantation in experimental in vitro and in vivo models 

2021 ◽  
Author(s):  
Natalia Bezdieniezhnykh ◽  
Alexandra Lykhova ◽  
Tamara Kozak ◽  
Taras Zadvornyi ◽  
Olena Voronina ◽  
...  
Keyword(s):  
Human Peripheral Blood ◽  
Clinical Manifestations ◽  
Peripheral Blood Lymphocytes ◽  
Model Systems ◽  
In Vivo Studies ◽  
In Vivo Models ◽  
Pharmacologically Active ◽  
Hydrophilic Gel

Abstract Background: The assessment of biosafety of pharmacologically active substances is crucial for determining the feasibility of their medical use. There are controversial issues regarding the use of substances of different origins as implants. Methods: We have conducted the comprehensive studies to determine the in vivo toxicity and in vitro genotoxicity of new generation of hydrophilic gel for implantation (production name of the substance "Activegel") to detail its characteristics and assess its biosafety. Results: In vivo studies have shown the absence of clinical manifestations of intoxication in animals and no abnormalities in their physiological condition, general and biochemical blood tests. Evaluation of the site of the gel application showed no inflammatory reaction and evidenced on normal state of tissues of animal skin. The results of the genotoxicity test indicated that the gel did not affect the parameters of DNA comets and, accordingly, had no genotoxic effect on human peripheral blood lymphocytes. When studying the effect of the gel on malignantly transformed cells in vitro, it was found that the gel for implantation did not change the proliferative activity and viability of human breast cancer cells. Conclusions: Comprehensive in vitro and in vivo study using various experimental model systems showed that the hydrophilic gel for implantation "Activegel" is non-toxic.

scholarly journals Nivalenol induced apoptosis in human peripheral blood lymphocytes in vitro and mouse peripheral blood lymphocytes in vivo

1997 ◽  
Vol 1997 (45) ◽  
pp. 33-37 ◽  
Author(s):  
Naoto YOSHINO ◽  
Mari TAKIZAWA ◽  
Hiroki OKUMURA ◽  
Tomomi IHARA ◽  
Masao SUGAMATA ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes ◽  
Human Peripheral Blood Lymphocytes ◽  
Induced Apoptosis

DNA damage and susceptibility to oxidative damage in lymphocytes: effects of carotenoidsin vitroandin vivo

2004 ◽  
Vol 91 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Siân B. Astley ◽  
David A. Hughes ◽  
Anthony J. A. Wright ◽  
Ruan M. Elliott ◽  
Susan Southon
Keyword(s):  
Oxidative Damage ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Plasma Concentrations ◽  
Peripheral Blood Lymphocytes ◽  
Repair Mechanisms ◽  
Oxidative Challenge ◽  
Β Carotene

Reports on the effects of carotenoids are conflicting. The present paper examines similarities and differences from contiguous studiesin vitroandin vivo. Single-cell gel electrophoresis was used to measure the frequency of single-strand breaks (SSB) in the cell line MOLT-17 (as a model system) and human peripheral blood lymphocytes (PBL). MOLT-17 cells were supplemented with β-carotene, lutein or lycopene at a range of concentrations (0·00–8·00 μmol/l) using a liposome delivery method. Uptake was dose-dependent. β-Carotene concentration in the media had no effect on SSB in control cells, but incubation with lycopene or lutein (>2·00 μmol/l) increased the numbers of SSB in control cells. MOLT-17 DNA was less susceptible to oxidative damage (100 μmol H2O2/l, 5 min, 4 °C) following incubation with carotenoids between 0·50 and 1·00 μmol/l; at >1·00 μmol/l the effects were ambiguous. Apparently healthy male volunteers supplemented their habitual diets with lutein, β-carotene or lycopene (natural isolate capsules, 15 mg/d, 4 weeks) in three independent studies, raising plasma concentrations to different extents. Lycopene and lutein had no effect on SSB in control PBL or following oxidative challenge. However, increased plasma β-carotene was associated with more SSB in control cells whilst PBL DNA resistance to oxidative damageex vivowas unaffected. These results suggest that the carotenoids are capable of exerting two overlapping but distinct effects: antioxidant protection by scavenging DNA-damaging free radicals and modulation of DNA repair mechanisms.

scholarly journals The Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cell Cytokinesis and Proliferation by Interacting with Translation Elongation Factor 1α

2008 ◽  
Vol 82 (14) ◽  
pp. 6962-6971 ◽  
Author(s):  
Bing Zhou ◽  
Junli Liu ◽  
Qiuna Wang ◽  
Xuan Liu ◽  
Xiaorong Li ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Human Peripheral Blood ◽  
Elongation Factor ◽  
Protein Translation ◽  
Peripheral Blood Lymphocytes ◽  
Atypical Pneumonia ◽  
Filamentous Actin ◽  
N Protein

ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, an emerging disease characterized by atypical pneumonia. Using a yeast two-hybrid screen with the nucleocapsid (N) protein of SARS-CoV as a bait, the C terminus (amino acids 251 to 422) of the N protein was found to interact with human elongation factor 1-alpha (EF1α), an essential component of the translational machinery with an important role in cytokinesis, promoting the bundling of filamentous actin (F-actin). In vitro and in vivo interaction was then confirmed by immuno-coprecipitation, far-Western blotting, and surface plasmon resonance. It was demonstrated that the N protein of SARS-CoV induces aggregation of EF1α, inhibiting protein translation and cytokinesis by blocking F-actin bundling. Proliferation of human peripheral blood lymphocytes and other human cell lines was significantly inhibited by the infection of recombinant retrovirus expressing SARS-CoV N protein.

Applications of Human Peripheral Blood Lymphocytes in Genotoxicity and Cytotoxicity

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 231-241
Author(s):  
Lucia Celotti ◽  
Vera Bianchi
Keyword(s):  
Cell Cycle ◽  
Peripheral Blood ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Human Peripheral Blood ◽  
Quantitative Difference ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes

A number of features make peripheral blood lymphocytes an excellent system for studying both genotoxicity and cytotoxicity in humans. They are an abundant and readily accessible source of somatic cells, mostly in a non-proliferative state, but able to be stimulated by mitogens to enter the cell cycle. The blastocyte transformation of lymphocytes is a useful model for investigating the mechanisms which regulate cell-cycle progression in mammalian cells. By stimulating lymphocytes in vitro, it is possible to detect the genetic damages they have sustained in vivo, which become manifest as chromosomal aberrations, sister-chromatid exchanges or gene mutations. The metabolic properties of lymphocytes have been extensively studied, especially with reference to their characteristic collection of enzymes involved in nucleotide turnover, which makes them exquisitely sensitive to changes in intracellular levels of DNA precursors. The data collected on the ability of lymphocytes to metabolise xenobiotics show a marked quantitative difference between resting and proliferating lymphocytes, and minor qualitative differences between lymphocytes and other cell types, e.g. hepatocytes. An indirect approach to detect the metabolism of genotoxic xenobiotics by lymphocytes is the analysis of DNA adducts in their chromatin after in vivo or in vitro exposure. Lymphocytes can be employed to identify the (cyto)genetic consequences of in vivo genotoxic exposure and inter-individual variation in sensitivity to genotoxic agents. The analysis of mutations at the hgprt locus in lymphocytes is a promising approach for the study of somatic-cell mutations in humans and of the possible mechanisms of in vivo selection against mutants. In the field of cytotoxicity, the applications of lymphocytes are, as yet, still few: the main effect measured is the impairment of the proliferative response to mitogens. But lymphocytes can be employed as primary human cells to be treated in vitro with mutagenic or toxic chemicals in standard genotoxicity and cytotoxicity assays, and offer the advantage of avoiding the problems of inter-species extrapolation of results by testing in a human system. Moreover, the (geno)toxic effects detected in lymphocytes after treatments in vitro may give information on the spontaneous or environmentally-determined susceptibility of the individual donors to xenobiotics.

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