Lymphokine and cytokine research最新文献

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The inducible expression of THP-1 cell interleukin-1 mRNA: effects of estrogen on differential response to phorbol ester and lipopolysaccharide. THP-1细胞白细胞介素-1 mRNA的诱导表达:雌激素对酚酯和脂多糖差异反应的影响。
Lymphokine and cytokine research Pub Date : 1994-02-01
G Shanker, M Sorci-Thomas, T C Register, M R Adams
{"title":"The inducible expression of THP-1 cell interleukin-1 mRNA: effects of estrogen on differential response to phorbol ester and lipopolysaccharide.","authors":"G Shanker,&nbsp;M Sorci-Thomas,&nbsp;T C Register,&nbsp;M R Adams","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Monokines, such as interleukin-1, have been implicated in the pathogenesis of several pathologic processes, including the initiation and progression of atherosclerosis. Since estrogen has been identified as a modulator of atherosclerosis progression, we sought to examine the effect of estrogen on the inducible expression of interleukin-1 beta (IL-1 beta) and interleukin-1 alpha (IL-1 alpha) mRNA in the monocytic cell line, THP-1. Cells were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) (50 ng/ml) for 48 or 96 h to induce differentiation. Some cells were treated with lipopolysaccharide (LPS) (10 micrograms/ml) in the last 3 h and/or 10(-9) M ethinyl estradiol (estrogen) in the last 20 h. Total cellular RNA was isolated, and cDNA was synthesized and amplified using the polymerase chain reaction (PCR) using two sets (pairs) of 32P-labeled primers, one for IL-1 beta (product size 388 bp) and the second for the internal control, beta-actin (1126 bp), or to detect another cytokine mRNA, a set of primers for IL-1 alpha (product size 420 bp) and beta-actin. The PCR products were separated on a 3.0% agarose gel and the ratio of radioactivity incorporated into cytokine PCR products and beta-actin products was determined to assess the relative changes in the relative levels of cytokine to beta-actin mRNA abundance in response to various inducers. Treatment with TPA for 48 h induced expression of IL-1 beta mRNA, an effect that was enhanced two fold by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19176649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effects of interleukin-10 on interleukin-1 receptor antagonist and interleukin-1 beta production in human monocytes and neutrophils. 白细胞介素-10对人单核细胞和中性粒细胞白细胞介素-1受体拮抗剂和白细胞介素-1 β生成的影响。
Lymphokine and cytokine research Pub Date : 1994-02-01
J K Jenkins, M Malyak, W P Arend
{"title":"The effects of interleukin-10 on interleukin-1 receptor antagonist and interleukin-1 beta production in human monocytes and neutrophils.","authors":"J K Jenkins,&nbsp;M Malyak,&nbsp;W P Arend","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>LPS stimulates human monocytes and neutrophils to produce IL-1 beta and IL-1 receptor antagonist (IL-1ra). IL-10 has been shown to inhibit LPS-induced IL-1 beta production in human monocytes. The objective of these studies was to examine the effects of IL-10 on human monocyte and neutrophil IL-1ra protein and mRNA production and compare it to IL-1 beta. IL-10 markedly inhibited LPS-induced IL-1 beta mRNA and protein production in both cell types. IL-10 alone induced IL-1ra mRNA production in monocytes with a low level of protein production. Furthermore, IL-10 led to enhanced levels of IL-1ra mRNA in LPS-induced monocytes at 2 to 6 h and of IL-1ra protein at 4-16 h, but there was no increase in levels of IL-1ra protein at 24 h or later. In neutrophils IL-10 alone did not stimulate IL-1ra protein or mRNA production and did not augment LPS-induced IL-1ra mRNA. These net effects of IL-10 resulted in an increase in the ratio of IL-1ra to IL-1 beta in both neutrophils and monocytes. The net effects of IL-10 on inflammatory cells may be important in modulation of biologic responses to IL-1.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 1","pages":"47-54"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19177201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Induction of cytokines by zinc ions in human peripheral blood mononuclear cells and separated monocytes. 锌离子诱导人外周血单核细胞和分离单核细胞的细胞因子。
Lymphokine and cytokine research Pub Date : 1994-02-01
C Driessen, K Hirv, L Rink, H Kirchner
{"title":"Induction of cytokines by zinc ions in human peripheral blood mononuclear cells and separated monocytes.","authors":"C Driessen,&nbsp;K Hirv,&nbsp;L Rink,&nbsp;H Kirchner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Zinc plays an important role in the maintenance of immune functions. The immunological mechanisms triggered by zinc, however, are still poorly understood. In our experiments Zn2+ ions, added as ZnSO4, stimulated PBMC to produce IFN-gamma, IL-1 beta, IL-6, TNF-alpha, and sIL-2R in a concentration-dependent manner. CuSO4 and CaCl2 as cation and anion controls had no effect. The optimal concentration of zinc was 0.5 mM for monokine induction and 0.25 mM for induction of IFN-gamma and sIL-2R. The highest IL-1 beta and IL-6 levels were found on day 2 and maximum TNF-alpha after 16 h. IFN-gamma and sIL-2R production were optimum after 6 and 7 days, respectively. Monokines could be induced in autologous serum as well as in fetal calf serum and serum-free medium. Enriched monocytes and the human monocyte cell line Mono Mac 6 also released IL-1 beta after zinc challenge. Anti-IL-6 reduced IFN-gamma secretion whereas anti-IL-1 beta inhibited it. These data suggest that zinc acts primarily on monocytes by inducing monokine secretion and that T-cell activation represents a secondary effect in the cytokine cascade.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 1","pages":"15-20"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19176650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interleukin-8 immunoreactivity in epidermis of cutaneous T-cell lymphoma patients. 皮肤t细胞淋巴瘤患者表皮白细胞介素-8免疫反应性。
Lymphokine and cytokine research Pub Date : 1994-02-01
J M Wismer, R C McKenzie, D N Sauder
{"title":"Interleukin-8 immunoreactivity in epidermis of cutaneous T-cell lymphoma patients.","authors":"J M Wismer,&nbsp;R C McKenzie,&nbsp;D N Sauder","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The histopathologic hallmark of cutaneous T-cell lymphoma is collections of malignant T cells in the epidermis. The mechanism(s) involved in the T-cell localization is unknown, however recent evidence suggests that cytokines play a role. Since Interleukin-8 functions both as a leukocyte and lymphocyte chemoattractant, we measured IL-8 expression in skin of cutaneous T-cell lymphoma patients. Lesional skin was obtained by biopsy from cutaneous T-cell lymphoma (CTCL) patients and patients suffering from other dermatoses and subjected to in situ hybridization with a 35S-Riboprobe and immunofluorescence to detect IL-8. Fourteen out of 15 lesional biopsies from histologically proven CTCL patients displayed intense epidermal IL-8 immunoreactivity compared to negligible reactivity in sections from 14 normal patients and other inflammatory dermatoses. These results were corroborated by strong hybridization signals using IL-8 probes in only the lesional CTCL skin. Lesional CTCL epidermis contains elevated levels of IL-8 mRNA and protein suggesting a role for this cytokine in the pathogenesis of the disease.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 1","pages":"21-7"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19177198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulation of IL-1 alpha expression in human keratinocytes: transcriptional activation of the IL-1 alpha gene by TNF-alpha, LPS, and IL-1 alpha. 人角质形成细胞中IL-1 α表达的调控:tnf - α、LPS和IL-1 α对IL-1 α基因的转录激活
Lymphokine and cytokine research Pub Date : 1994-02-01
K Kameda, K Sato
{"title":"Regulation of IL-1 alpha expression in human keratinocytes: transcriptional activation of the IL-1 alpha gene by TNF-alpha, LPS, and IL-1 alpha.","authors":"K Kameda,&nbsp;K Sato","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epidermal epithelial cells (keratinocytes) produce IL-1 alpha potentially relevant for mechanisms of microbial invasion, inflammation, immunological reactions, and tissue injury in the skin. We investigated the regulation of IL-1 alpha expression by human keratinocytes. RIA showed that TNF-alpha, LPS, and PMA caused a marked accumulation of IL-1 alpha Ag in keratinocyte lysates and supernatants after 2 h of exposure. Northern blot analyses demonstrated that TNF-alpha, IL-1 alpha, and LPS transiently increased the steady-state levels of IL-1 alpha mRNA by 8-fold, 10-fold, and 6-fold, respectively, at 2 h. Nuclear run-on transcription studies with isolated nuclei from cells treated with TNF-alpha, IL-1 alpha, and LPS showed that the transcription rate of the IL-1 alpha gene increased 6-fold, 6.5-fold, and 4-fold, respectively, after 2 h of treatment. PMA led to a more sustained accumulation of IL-1 alpha mRNA and had no effect on the transcription rate of the IL-1 alpha gene. The 5' region of the IL-1 alpha gene between base pairs -105 and +724 was linked to the luciferase reporter gene and used in transient expression studies. LPS stimulated luciferase activity from the chimeric gene, suggesting that the 5' region of the IL-1 alpha gene tested may, in part, include a responsive sequence to LPS.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 1","pages":"29-35"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19177199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Positive and negative selection for tumor necrosis factor responsiveness reveals an inhibitory role for EGF receptor in TNF-induced antiproliferation. 肿瘤坏死因子反应性的阳性和阴性选择揭示了EGF受体在tnf诱导的抗增殖中的抑制作用。
Lymphokine and cytokine research Pub Date : 1994-02-01
K Nishikawa, J Rotbein, D Vijjeswarapu, L Owen-Schaub, M G Rosenblum, N J Donato
{"title":"Positive and negative selection for tumor necrosis factor responsiveness reveals an inhibitory role for EGF receptor in TNF-induced antiproliferation.","authors":"K Nishikawa,&nbsp;J Rotbein,&nbsp;D Vijjeswarapu,&nbsp;L Owen-Schaub,&nbsp;M G Rosenblum,&nbsp;N J Donato","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tumor necrosis factor (TNF) induces dose-dependent, but incomplete cytotoxicity in ME-180 cervical carcinoma cells resulting in a significant reduction in cell viability. In this cell line there exists a characteristic residual tumor cell population that appears to be resistant to TNF. In order to investigate tumor cell heterogeneity and characteristics that correlate with their escape from TNF-induced cytotoxicity, TNF-resistant ME-180 cell variants (ME-180R) were isolated from a population of ME-180 cervical carcinoma cells (ME-180 parental). Incubation of ME-180 parental cells with TNF resulted in measurable changes in tumor cell DNA structural integrity and dose-dependent cytotoxicity, whereas ME-180R cell growth and DNA integrity were not effected by incubation with TNF. Binding of 125I-labeled TNF to a TNF-specific cell-surface receptor was measurable and equivalent on both ME-180R and ME-180 parental cells and both cell lines predominantly expressed the p55 form of the TNF receptor based upon flow cytometric analysis. Although both cell lines shared similar doubling times, intrinsic EGF receptor tyrosine kinase activity in ME-180R cells was found to be > 3-fold higher than that isolated from ME-180 parental cells. These results suggest that TNF-responsiveness may be mediated at a point subsequent to TNF binding and may be regulated, in part, by the expression of tyrosine kinase activity. To further explore this hypothesis, A431 vulvular carcinoma cells that express resistance to TNF were cloned and variants were isolated that escaped EGF-induced growth inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 1","pages":"37-45"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19177200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulatory effects of T cell lymphokines on cytokine gene expression in monocytes. T细胞淋巴因子对单核细胞细胞因子基因表达的调控作用。
Lymphokine and cytokine research Pub Date : 1993-12-01
F H Cluitmans, B H Esendam, J E Landegent, R Willemze, J H Falkenburg
{"title":"Regulatory effects of T cell lymphokines on cytokine gene expression in monocytes.","authors":"F H Cluitmans,&nbsp;B H Esendam,&nbsp;J E Landegent,&nbsp;R Willemze,&nbsp;J H Falkenburg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hematopoiesis is regulated by colony-stimulating factors (CSF) and many other cytokines. T helper cell and monocyte/macrophage interactions that take place in the immune response, resulting in the production of many cytokines, probably can influence inducible hematopoiesis. We investigated the effect of the T helper cell-derived lymphokines IL-2, IL-3, GM-CSF, and IFN-gamma, on the expression of cytokine genes in monocytes and compared this to LPS-induced cytokine gene expression in monocytes. To avoid inadvertent activation of monocytes, cells were purified by elutriation and cultured under serum-free, LPS-free, and nonadherent conditions. Similar to LPS, IL-2, IL-3, and GM-CSF induced the expression of IL-1 beta, IL-6, IL-8, TNF-alpha, and IL-1-RA genes in monocytes, but with some differences in the amount and kinetics of cytokine mRNA accumulation. Unlike LPS, IL-2, IL-3, and GM-CSF did not induce G-CSF and GM-CSF gene expression in monocytes. GM-CSF and IL-3 were the only inducers capable of expressing the M-CSF gene in monocytes. IL-2, IL-3, and GM-CSF showed no effect on the IL-10 gene while IFN-gamma appeared to have no effect on any of the cytokine genes studied in monocytes. These data indicate that in the immune response expression of the proinflammatory cytokine genes, IL-1 beta, IL-6, IL-8, and TNF-alpha, can occur and that autoregulatory control mechanisms, like the expression of IL-1-RA gene, are also activated.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 6","pages":"457-64"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19117217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cytokine production by T-cell lines derived from tumor-infiltrating lymphocytes from patients with ovarian carcinoma: tumor-specific immune responses and inhibition of antigen-independent cytokine production by ovarian tumor cells. 卵巢癌患者肿瘤浸润淋巴细胞衍生的t细胞系产生的细胞因子:肿瘤特异性免疫反应和卵巢肿瘤细胞对抗原非依赖性细胞因子产生的抑制
Lymphokine and cytokine research Pub Date : 1993-12-01
S Kooi, R S Freedman, J Rodriguez-Villanueva, C D Platsoucas
{"title":"Cytokine production by T-cell lines derived from tumor-infiltrating lymphocytes from patients with ovarian carcinoma: tumor-specific immune responses and inhibition of antigen-independent cytokine production by ovarian tumor cells.","authors":"S Kooi,&nbsp;R S Freedman,&nbsp;J Rodriguez-Villanueva,&nbsp;C D Platsoucas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The ability of T-cell lines derived from tumor-infiltrating lymphocytes (TIL) from patients with ovarian carcinoma to produce interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and IL-6 in response to autologous or allogeneic ovarian carcinoma tumor cells was determined. These T-cell lines were derived in low concentrations of recombinant IL-2 (rIL-2), 200 IU/ml. Certain of these T-cell lines (3 of 7) exhibited antigen-independent (spontaneous) production of moderate to low concentrations of IFN-gamma (75 to 112 pg/ml), TNF-alpha (62-88 pg/ml), and IL-6 (38 to 690 pg/ml), in culture medium alone in the absence of rIL-2, tumor cells or polyclonal activators. Addition of 20 IU/ml of rIL-2 to the cultures resulted in a significant increase of the antigen-independent production of IFN-gamma (range 75-6480 pg/ml) by all seven T-cell lines and TNF-alpha (44-490 pg/ml) by 5 of 7 T-cell lines. Certain T-cell lines (4 of 7) exhibited antigen-independent production of IL-6 (38-690 pg/ml), which was not affected by the addition of 20 IU/ml of rIL-2. Certain TIL-derived T-cell lines (2 of 7) produced IFN-gamma, TNF-alpha, and IL-6 in response to stimulation with autologous ovarian tumor cells, in the presence of 20 IU/ml of rIL-2. Irradiated autologous ovarian tumor cells alone or in the presence of rIL-2 did not produce any detectable levels of IFN-gamma, TNF-alpha, or IL-6 during the 6 day culture.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 6","pages":"429-37"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19115865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunostaining of interleukin-4 receptor on human renal cell carcinoma. 白细胞介素-4受体在人肾细胞癌中的免疫染色研究。
Lymphokine and cytokine research Pub Date : 1993-12-01
F Varricchio, N I Obiri, G P Haas, R K Puri
{"title":"Immunostaining of interleukin-4 receptor on human renal cell carcinoma.","authors":"F Varricchio,&nbsp;N I Obiri,&nbsp;G P Haas,&nbsp;R K Puri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Immunocytochemistry on three primary cultures of RCC tumor cells and immunohistochemistry on five frozen sections of RCC were performed by utilizing a monoclonal antibody (M-57) to human IL-4R. We found that all three RCC tumor cell cytospin preparations stained with anti-IL-4R monoclonal antibody. Tumor cells stained with IgG control did not show any staining. Similarly, five histologically proven RCC frozen sections prepared from nephrectomy specimens had moderate to intense immunoreactivity to IL-4 receptor antibody. RCC sections stained with normal mouse IgG2b showed only background type staining. Frozen section prepared from uninvolved kidney showed only nonspecific staining. A flow cytometric analysis of primary cultures of RCC tumor cells confirmed the immunohistochemical data and showed that almost all of the cells were positive for IL-4 receptor expression. These results demonstrate that human RCC express immunoreactive IL-4 receptors, which may be a target for diagnosis and therapy by an anti-IL-4 receptor antibody fused to toxins or radionuclides or alternatively by IL-4 toxins.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 6","pages":"465-9"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19117218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cadmium induces interleukin-8 production in human peripheral blood mononuclear cells with the concomitant generation of superoxide radicals. 镉诱导人外周血单核细胞产生白细胞介素-8,同时产生超氧自由基。
Lymphokine and cytokine research Pub Date : 1993-12-01
H Horiguchi, N Mukaida, S Okamoto, H Teranishi, M Kasuya, K Matsushima
{"title":"Cadmium induces interleukin-8 production in human peripheral blood mononuclear cells with the concomitant generation of superoxide radicals.","authors":"H Horiguchi,&nbsp;N Mukaida,&nbsp;S Okamoto,&nbsp;H Teranishi,&nbsp;M Kasuya,&nbsp;K Matsushima","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acute or chronic exposure to cadmium (Cd) causes severe organ damages with the infiltration of leukocytes, neutrophils in particular occurring in the acute phase. Interleukin-8 (IL-8), a novel neutrophil chemotactic and activating cytokine, is produced by various types of cells in response to a wide variety of inflammatory stimuli. The administration of an antibody against IL-8 has been shown to inhibit neutrophil infiltration in several animal models, indicating a causal relationship between IL-8 and neutrophil infiltration. Hence, in this study we investigated whether Cd induced IL-8 production in human peripheral blood mononuclear cells (PBMC). Cd, over a wide range of concentrations, did induce human PBMC to produce large amounts of bioactive IL-8, the maximal induction being observed at 10(-4) M. The production was inhibited specifically by a metal chelating agent, ethylenediaminetetraacetic acid (EDTA). Steady level of IL-8 mRNA increased within 30 min after the addition of Cd and reached a maximal level at 2 h, decreasing thereafter. A protein synthesis inhibitor, cycloheximide, failed to inhibit IL-8 mRNA accumulation, indicating that new protein synthesis was not required for IL-8 mRNA induction. Concomitantly with the induction of IL-8, within 10 min Cd generated reactive oxygen intermediates (ROI) in human PBMC. A radical scavenger, N-acetyl-L-cysteine (NAC), inhibited both IL-8 production and the generation of ROI, implying the possible involvement of ROI in IL-8 production. This notion was also supported by our findings that a superoxide generating agent, paraquat, induced IL-8 production in human PBMC and that NAC blocked this paraquat-induced IL-8 production.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"12 6","pages":"421-8"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19115863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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