Lymphokine and cytokine research最新文献_第4页

Mechanisms involved in the processing of the p55 and the p75 tumor necrosis factor (TNF) receptors to soluble receptor forms. p55和p75肿瘤坏死因子(TNF)受体转化为可溶性受体的机制。

Lymphokine and cytokine research Pub Date : 1994-06-01

F Björnberg, M Lantz, I Olsson, U Gullberg

{"title":"Mechanisms involved in the processing of the p55 and the p75 tumor necrosis factor (TNF) receptors to soluble receptor forms.","authors":"F Björnberg, M Lantz, I Olsson, U Gullberg","doi":"","DOIUrl":"","url":null,"abstract":"The two tumor necrosis factor (TNF) receptors (TNF-R55 and TNF-R75) can release soluble TNF-binding proteins (TNF-R55-BP and TNF-R75-BP) by proteolytic cleavage. The proteolytic processing of the TNF receptors was investigated in monoblastic THP-1 and promyelocytic HL-60-10 leukemic cell lines. The release of soluble forms of both receptors was rapidly stimulated by staurosporine-sensitive protein kinase C activation by phorbol myristate acetate (PMA) and more slowly stimulated by TNF. No receptor release was seen below a temperature of 16 degrees C. NH4Cl (10 mmol/liter) and monensin (1 mumol/liter), known to increase intracellular pH, inhibited to some extent PMA- and TNF-induced release of both TNF-R55-BP and TNF-R75-BP. The inhibitory effect of monensin might be explained by a diminished translocation of newly synthesized receptor to the plasma membrane. The weak inhibitory effect of NH4Cl on PMA-induced release of soluble receptor forms could be due to effects on a pH-sensitive compartment. PMA-induced down-regulation of receptors was not dependent on acidity as it occurred also in the presence of monensin and NH4Cl when the release of TNF-BPs is partially blocked. Dibutyryl cAMP inhibited the PMA-induced release of TNF-R55-BP but not of TNF-R75-BP in both cell lines investigated. In addition, dibutyryl cAMP alone stimulated the release of both receptors but only in THP-1 cells. Our data show that the generation of soluble forms of both TNF receptors can be regulated by both PKC and PKA.","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 3","pages":"203-11"},"PeriodicalIF":0.0,"publicationDate":"1994-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18947808","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

Identification of an epitope of tumor necrosis factor (TNF)-receptor type 1 (p55) recognized by a TNF-alpha-antagonist monoclonal antibody. TNF α拮抗剂单克隆抗体识别的肿瘤坏死因子(TNF)受体1型(p55)表位的鉴定

Lymphokine and cytokine research Pub Date : 1994-06-01

A Corti, L Bagnasco, G Cassani

{"title":"Identification of an epitope of tumor necrosis factor (TNF)-receptor type 1 (p55) recognized by a TNF-alpha-antagonist monoclonal antibody.","authors":"A Corti, L Bagnasco, G Cassani","doi":"","DOIUrl":"","url":null,"abstract":"The relationships between epitope topography and agonistic/antagonistic effects of anti-TNF receptor type 1 (TNF-R1) antibodies on TNF-alpha cytotoxic activity have been studied. To this purpose various monoclonal antibodies (mAbs) against the soluble form of TNF-R1 (sTNF-R1) have been generated and characterized. Epitope topography studies identified at least four distinct epitopes located outside (4E10) or within (or close to) the TNF-alpha binding site of urinary sTNF-R1 (7H3, 4C1, 9B11). mAbs 7H3 and 4C1 were able to neutralize the inhibition of human TNF-alpha cytotoxicity on L-M cells by sTNF-R1, while 4E10 was unable. Moreover, 7H3 and 4C1 were able to antagonize the TNF-alpha cytotoxicity on human U937 cells, while they were uneffective on mouse L-M cells, suggesting that these antibodies recognize, in a species-specific mode, also the membrane form of the human receptor. No agonistic effects were observed when these antibodies were used in the absence of TNF-alpha. Epitope topography studies carried out using overlapping decapeptides covering most of the sTNF-R1 sequence showed that residues 143-148 of the fourth cysteine-rich domain of the receptor (FFLREN) contain antigenic determinants recognized by the antagonist antibody 7H3. These results suggest that at least part of residues 143-148 of sTNF-R1 are surface exposed on the soluble as well as on the membrane forms of TNF-R1 and are accessible to TNF-alpha antagonists.","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 3","pages":"183-90"},"PeriodicalIF":0.0,"publicationDate":"1994-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18533238","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

Effects of TNF, IL-1, and the combination of both cytokines on cholesterol metabolism in Syrian hamsters. TNF、IL-1及两种细胞因子联合对叙利亚仓鼠胆固醇代谢的影响

Lymphokine and cytokine research Pub Date : 1994-06-01

I Hardardóttir, A H Moser, R Memon, C Grünfeld, K R Feingold

{"title":"Effects of TNF, IL-1, and the combination of both cytokines on cholesterol metabolism in Syrian hamsters.","authors":"I Hardardóttir, A H Moser, R Memon, C Grünfeld, K R Feingold","doi":"","DOIUrl":"","url":null,"abstract":"Infection and inflammation are associated with alterations in lipid metabolism that may be mediated by cytokines such as TNF and IL-1. This study determined the effects of TNF and IL-1 on certain aspects of cholesterol metabolism. TNF or IL-1 administration to Syrian hamsters increased serum cholesterol levels by 17 and 21%, respectively, and decreased HDL cholesterol levels by 20 and 15%, respectively. TNF + IL-1 increased serum cholesterol levels by 58% and decreased HDL cholesterol levels by 58%. TNF or IL-1 increased hepatic HMG CoA reductase mRNA levels by 3.5- and 3-fold, respectively. TNF + IL-1 increased HMG CoA reductase mRNA levels by 7-fold. IL-1 increased hepatic LDL receptor mRNA levels by 2-fold while TNF and a combination of TNF + IL-1 had minimal effects. TNF or IL-1 did not affect hepatic apo E or apo A-I mRNA levels while a combination of TNF + IL-1 decreased both mRNA levels by 50%. Our results demonstrate that TNF and IL-1 similarly affect the parameters of cholesterol metabolism studied. Furthermore, the combination of TNF + IL-1 was, in most cases, more effective than either cytokine alone, and reproduced many of the effects of LPS.","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 3","pages":"161-6"},"PeriodicalIF":0.0,"publicationDate":"1994-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18943334","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-1 down-regulates type I interleukin 1 receptor mRNA expression in a human fibroblast cell line TIG-1 in the absence of prostaglandin E2 synthesis. 在前列腺素E2合成缺失的情况下，白细胞介素1下调人成纤维细胞系TIG-1中I型白细胞介素1受体mRNA的表达。

Lymphokine and cytokine research Pub Date : 1994-06-01

T Takii, H Hayashi, T Marunouchi, K Onozaki

{"title":"Interleukin-1 down-regulates type I interleukin 1 receptor mRNA expression in a human fibroblast cell line TIG-1 in the absence of prostaglandin E2 synthesis.","authors":"T Takii, H Hayashi, T Marunouchi, K Onozaki","doi":"","DOIUrl":"","url":null,"abstract":"We have shown that interleukin-1 (IL-1) up-regulates transcription of its own receptor and number of cell surface IL-1 receptor (IL-1R) type I molecule through induction of prostaglandin E2 (PGE2) synthesis and subsequent intracellular cAMP accumulation in a human lung fibroblast cell line (TIG-1). In this study, the effect of IL-1 on IL-1R mRNA expression was investigated in the absence of PGE2 synthesis. In the presence of indomethacin, an inhibitor of cyclooxygenase, IL-1 inhibited the expression of IL-1R mRNA within 4 h after treatment, and the inhibition sustained at least for 24 h. IL-1 beta as well as IL-1 alpha at higher than 1 U/ml exhibited the inhibitory effect. The inhibitory effect of IL-1 was inhibited by cycloheximide suggesting that de novo protein synthesis is required. IL-1 appeared to destabilize IL-1R mRNA within 30 min after treatment of the cells. Furthermore, this effect of IL-1 was not observed in a synthetic medium and was dependent on serum concentrations indicating that a serum component(s) is involved. These results indicate that IL-1 regulates IL-1R mRNA expression in both a positive and negative manner, and that the negative effect represents a negative feedback mechanism.","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 3","pages":"213-9"},"PeriodicalIF":0.0,"publicationDate":"1994-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18947809","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

Essential involvement of interleukin-8 in neutrophil recruitment in rabbits with acute experimental arthritis induced by lipopolysaccharide and interleukin-1. 白细胞介素-8在脂多糖和白细胞介素-1诱导的兔急性实验性关节炎中性粒细胞募集中的重要作用。

Lymphokine and cytokine research Pub Date : 1994-04-01

T Akahoshi, H Endo, H Kondo, S Kashiwazaki, T Kasahara, N Mukaida, A Harada, K Matsushima

引用次数: 0

Effects of a novel topical immunomodulator, imiquimod, on keratinocyte cytokine gene expression. 一种新的局部免疫调节剂咪喹莫特对角质细胞细胞因子基因表达的影响。

Lymphokine and cytokine research Pub Date : 1994-04-01

T Kono, S Kondo, S Pastore, G M Shivji, M A Tomai, R C McKenzie, D N Sauder

{"title":"Effects of a novel topical immunomodulator, imiquimod, on keratinocyte cytokine gene expression.","authors":"T Kono, S Kondo, S Pastore, G M Shivji, M A Tomai, R C McKenzie, D N Sauder","doi":"","DOIUrl":"","url":null,"abstract":"A novel immunomodulator, imiquimod, has been shown to be an effective topical antiviral and antitumor agent in animal models. Imiquimod has been reported to induce interferon-alpha and other cytokines in animals and humans, but its precise role as an immunomodulator at skin sites has not been determined. We investigated its effect on cytokine gene expression in the human epidermal carcinoma cell line COLO-16 and human keratinocytes. COLO-16 cells were incubated with imiquimod (1 and 10 micrograms/ml) and human keratinocytes with 5 micrograms/ml for 6 or 24 h. Cytokine gene expression was analyzed by reverse-transcriptase PCR. In COLO-16 cells, imiquimod stimulated IL-6 mRNA levels 2.3- and 4.4-fold at 1 and 10 micrograms/ml after 6 h. IL-8 mRNA increased 4-fold at both 1 and 10 micrograms/ml. At 24 h, though IL-6 mRNA level at 1 micrograms/ml was further stimulated, enhanced expressions of IL-8 at 1 micrograms/ml and both IL-6 and IL-8 at 10 micrograms/ml were down-regulated. In human keratinocytes, 5 micrograms/ml of imiquimod stimulated IL-6 mRNA levels 1.4-fold at 6 h and 2.1-fold at 24 h, and IL-8 mRNA levels 1.7- and 2.0-fold at 6 and 24 h. IL-1 alpha mRNA levels in COLO-16 or keratinocytes were unchanged by either dose or incubation time. These results suggest that stimulation of IL-6 and IL-8 expression may be involved in the immunomodulating action of imiquimod.","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 2","pages":"71-6"},"PeriodicalIF":0.0,"publicationDate":"1994-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19054680","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

Identification of distinct sites of beta-endorphin that stimulate lymphokine production by murine CD4+ T cells. 通过小鼠CD4+ T细胞刺激淋巴因子产生的-内啡肽不同位点的鉴定。

Lymphokine and cytokine research Pub Date : 1994-04-01

P Van den Bergh, J Rozing, L Nagelkerken

{"title":"Identification of distinct sites of beta-endorphin that stimulate lymphokine production by murine CD4+ T cells.","authors":"P Van den Bergh, J Rozing, L Nagelkerken","doi":"","DOIUrl":"","url":null,"abstract":"We recently demonstrated that the opioid peptide beta-endorphin (beta-End) has the capacity to stimulate interleukin-2 (IL-2) and IL-4 production by murine CD4+ T cells. Since opioid peptides have been demonstrated to contain stimulatory as well as inhibitory sites, we studied peptide fragments of beta-End to identify a moiety with exclusive stimulatory capacity. To this end, the effects of various opioid peptides on the production of IL-2, IL-4, IL-6, and interferon-gamma (IFN-gamma) by CD4+ T cells were determined. It appeared that two peptide fragments of beta-End, i.e., beta-End6-31 and beta-End18-31, that lack the N-terminal enkephalin part, enhanced IL-2 and IL-4 production to a similar extent as intact beta-End, indicating that the N-terminal part is not involved in the stimulating effects of beta-End. Also the production of IL-6 and IFN-gamma was increased by these peptides. By contrast, the fragments beta-End24-31 and beta-End28-31 did not stimulate the production of the cytokines. Surprisingly, also alpha-End, which is equivalent to beta-End1-16 and hence lacks the sequence comprising amino acids 18 through 31, was stimulatory. This effect was not prevented by naloxone, indicating that opioid receptors were not involved. Moreover, methionine-enkephalin (Met-Enk), which binds to opioid receptors, did not affect cytokine production. Because both alpha-End and beta-End18-31 stimulate cytokine production by CD4+ T cells and do not overlap is sequence, it is concluded that at least two distinct sites of beta-End can exert stimulating effects on cytokine production.","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 2","pages":"63-9"},"PeriodicalIF":0.0,"publicationDate":"1994-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18914385","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

Expression of complete human IFN-gamma receptor and its extracellular domain in insect cells: purification and characterization of the recombinant proteins. 在昆虫细胞中表达完整的人类 IFN-gamma 受体及其胞外结构域：重组蛋白的纯化和特征。

Lymphokine and cytokine research Pub Date : 1994-04-01

D Moosmayer, E Gerlach, H Böttinger, P Scheurich, K Pfizenmaier

引用次数: 0

Sequential TNF and TGF-beta regulation of expansion and induction of cytotoxicity in long-term cultures of lymphokine-activated killer cells. 在淋巴因子激活的杀伤细胞长期培养中，顺序TNF和tgf - β调节增殖和诱导细胞毒性。

Lymphokine and cytokine research Pub Date : 1994-04-01

J Koberda, D Przepiorka, R P Moser, E E Grimm

{"title":"Sequential TNF and TGF-beta regulation of expansion and induction of cytotoxicity in long-term cultures of lymphokine-activated killer cells.","authors":"J Koberda, D Przepiorka, R P Moser, E E Grimm","doi":"","DOIUrl":"","url":null,"abstract":"Therapeutic use of lymphokine-activated killer (LAK) cells frequently requires higher numbers of effector cells than can be produced in short-term cultures. Extended stimulation of these cells by interleukin-2 (IL-2) past 2 weeks leads to a decrease in cytolytic activity and cell proliferation. To determine how known regulatory cytokines are involved in the mechanism responsible for loss lf IL-2 responsiveness, adherent LAK (A-LAK), nonadherent LAK (NA-LAK), monocyte-depleted (MD-LAK), and unmanipulated LAK (UN-LAK) cells derived from human peripheral blood were stimulated with high-dose IL-2 for 4 weeks, and cytokine production was measured serially. Despite continued supplementation with IL-2, cell number plaeaued at 2 weeks with a 2.5-3.0 log increase in A-LAK cultures and a 1.0 log increase in NA-LAK, MD-LAK, and UN-LAK cultures. Cytolytic activity had decreased significantly in all four culture systems after only 14 days of stimulation with IL-2 as assessed by the chromium release assay using K562, Daudi, and RP-mel tumor cell lines as targets, and LAK activity was barely detectable after 28 days of stimulation. Bioactive tumor necrosis factor (TNF) was present in concentrations of 15-55 U/ml during the first week of culture and at less than 10 U/ml thereafter. Bioactive transforming growth factor-beta (TGF-beta) was detected at 1-36 U/ml from 5 to 14 days of culture and decreased thereafter. Immunoreactive TGF-beta 2 was still present at concentrations of 20-90 pg/ml after 21 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 2","pages":"139-45"},"PeriodicalIF":0.0,"publicationDate":"1994-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19054785","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-4 enhances murine bone marrow macrophage M-CSF receptor expression by a posttranscriptional mechanism. 白细胞介素-4通过转录后机制增强小鼠骨髓巨噬细胞M-CSF受体的表达。

Lymphokine and cytokine research Pub Date : 1994-04-01

R Gibbons, F P Ross, S L Perkins, D L Lacey, J Martin, R Ebner, S L Teitelbaum, A J Kahn

{"title":"Interleukin-4 enhances murine bone marrow macrophage M-CSF receptor expression by a posttranscriptional mechanism.","authors":"R Gibbons, F P Ross, S L Perkins, D L Lacey, J Martin, R Ebner, S L Teitelbaum, A J Kahn","doi":"","DOIUrl":"","url":null,"abstract":"Activated T-lymphocytes secrete interleukin-4 (IL-4), which has been shown to modulate a variety of monocyte activities requiring monocyte/macrophage colony-stimulating factor (M-CSF). To account for this interaction, we postulated that IL-4 acts on target cells by altering the expression of the M-CSF receptor (M-CSFr). To test this hypothesis, murine bone marrow macrophages were cultured under conditions that down-regulate M-CSFr and the effect of IL-4 on the reexpression of the receptor measured by binding of 125I-labeled M-CSF to the cells. The data show that incubation with IL-4 results in a dose-dependent, 2-3 x increase in M-CSFr with no change in binding affinity and a maximal effect on binding at about 12 h. This increase in M-CSFr is dependent upon new, specific protein synthesis as shown by the inhibitory action of cycloheximide, and gel analysis of radiolabeled, specific protein, immunoprecipitated with anti-M-CSFr antibody. Treatment with IL-4 does not stimulate M-CSFr mRNA expression but, consistent with enhanced receptor levels, does result in a heightened proliferative response to M-CSF. Thus, IL-4 affects M-CSF treated monocytic cells, at least in part, by altering the expression of M-CSFr.","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 2","pages":"85-92"},"PeriodicalIF":0.0,"publicationDate":"1994-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19054682","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