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1.
Huang CD Ammit AJ Tliba O Kuo HP Penn RB Panettieri RA Amrani Y 《Journal of biomedical science》2005,12(5):763-776
Summary Using thapsigargin (Tg), an agent that mobilizes calcium by directly emptying intracellular stores, we previously showed that
intracellular calcium may play an important role in the regulation of intercellular adhesion molecule (ICAM)-1 gene expression
induced by cytokines in human airway smooth muscle (ASM) cells. In the present study, we extended this previous observation
by comparing the effect of Tg and other calcium-mobilizing G-protein-coupled receptor (GPCR) agonists on the expression of
different pro-inflammatory genes in response to tumor necrosis factor (TNF)-α in ASM cells. We found that in resting cells,
Tg (10–100 nM) or the bradykinin (BK) (1–10 μM) and thrombin (Thr) (1 U/ml) stimulated interleukin (IL)-6 secretion but had
no effect on regulated on activation, normal T cells expressed and secreted (RANTES) levels. More importantly, such calcium-mobilizing
agents significantly enhanced TNF-α-induced IL-6 secretion while RANTES secretion was abrogated. The use of luciferase-tagged
IL-6 and RANTES promoter constructs demonstrated similar effects of Tg on IL-6 and RANTES genes in basal and TNF-α-stimulated
conditions. The cyclic adenosine monophosphate (cAMP)-dependent pathway plays a minor role in this differential regulation
of IL-6 and RANTES genes expression. 2-Aminoethoxydiphenyl borate (APB), a blocker of store-operated calcium channels (SOCs),
and bisindolylmaleimide I (Bis I), a broad-spectrum protein kinase C (PKC) inhibitor, inhibited the basal and synergic effects
of IL-6 secretion in response to calcium-mobilizing agents and TNF-α, but did not prevent the abrogated effect of RANTES secretion.
We also found that Go-6976, a selective calcium-dependent PKC isozyme inhibitor, did not inhibit IL-6 secretion in response
to GPCR agonist and TNF-α; whereas Rottlerlin, a PKC-δ inhibitor, inhibited both Thr- and TNF-α-induced expression of IL-6,
while BK-induced IL-6 secretion was not affected. Interestingly, TNF-α-induced interferon regulatory factor (IRF)-1 activation
was significantly inhibited by all calcium-mobilizing agents, BK, Thr and Tg. These results show that calcium-mobilizing GPCR
agonists functionally interact with TNF-α to differentially regulate pro-inflammatory genes expression in human ASM cells,
possibly by involving Tg-sensitive intracellular calcium stores, SOC and PKC. 相似文献
2.
Andrew M. Jackson Anton B. Alexandrov S. Prescott Keith James 《Cancer immunology, immunotherapy : CII》1995,40(2):119-124
Intravesical immunotherapy for bladder cancer is the most effective form of tumour immunotherapy. Following repeated instillations
of bacillus Calmette-Guérin (BCG) organisms into the bladder large 0quantities of several cytokines are detected in the urine.
These cytokines include interleukins IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor α (TNFα), interferon γ (IFNγ)
and also soluble intercellular adhesion molecule ICAM-1. In the work reported here we simultaneously quantified urinary levels
of TNFα, TNFβ, TNF receptor I and TNF receptor II by enzyme-linked immunosorbent assay (ELISA) techniques and compared this
with bioactive levels of TNF. This was undertaken with a limited number of patients throughout a course of six instillations
of immuno therapy. Sequential instillations of BCG induced secretion of TNFα and TNFβ into urine. These cytokines were not
always secreted simultaneously, perhaps suggesting differential regulation of their synthesis. Maximal concentrations of TNFα
were 675 pg/ml and TNFβ 47 pg/ml. High levels of both species of soluble TNF receptor were readily identified in urine. Maximal
levels of sTNF-RI were 6200 pg/ml (range from 0) and for sTNF-RII 7800 pg/ml (range from 0). Contrasting with earlier published
observations concerning cytokine levels, the concentration of soluble receptor did not increase with repeated instillation.
In apparent contrast with the ELISA data, very low levels of bioactive TNF were identified by the L929 bioassay (maximum concentration
1 U/ml) despite the elevated concen t ration of immunoreactive TNF. The large concentrations of soluble TNF receptor in patients’
urine samples could account for the apparently low bioactivity as determined by the L929 cytotoxicity assay. The precise nature
of the role of TNF in BCG immunotherapy remains undetermined; however, it is thought that proinflammatory cytokines are in
part responsible for the clinical efficacy of this therapeutic approach. Whether other cytokines are antogonised by soluble
binding proteins remains to be determined. Furthermore, whether TNF is bioactive in the bladder wall and only neutralised
in the urine also requires investigation.
Received: 24 August 1994 / Accepted: 17 October 1994 相似文献
3.
Yao Z Qiu S Wang L Lu R Zhou CL Zhao PP Li HQ Gao WY 《Cancer immunology, immunotherapy : CII》2006,55(1):56-60
Tyroserleutide (YSL) is a type of active, low molecular weight polypeptide, comprised of three amino acids, which has antitumor
effects. YSL has various advantages over the other bioactive peptides such as its low molecular weight, simple construction,
nonimmunogenicity, specificity, few side effects, and ease of synthesis. However, the biological activities contributing to
it’s antitumor effects are not yet known. We studied the effects of YSL on the in vitro cytotoxic activity of BALB/c mice
peritoneal macrophages (PEMφ) against the target tumor cell lines BEL-7402 and B16-F10. We also measured the concentrations
of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and nitric oxide (NO) produced by YSL-activated Mφ, and we determined
the concentrations of IL-1β and NO secreted by YSL-activated murine macrophage RAW264.7 cells. YSL activated Mφ in vitro,
inhibited BEL-7402 proliferation, enhanced PEMφ antitumor effects, and stimulated IL-1β, TNF-α, and NO production by RAW264.7
cells. These data suggest that YSL activates the monocyte–macrophage system, which enhances Mφ antitumor effects against BEL-7402
and B16-F10 cells and stimulates the secretion by Mφ of cytotoxic effectors such as IL-1β, TNF-α, and NO. 相似文献
4.
5.
PPAR-α Expression Inversely Correlates with Inflammatory Cytokines IL-1β and TNF-α in Aging Rats 总被引:3,自引:0,他引:3
Dehydroepiandrosterone (DHEAS) was given the name “fountain of youth” in reference to its beneficial properties in memory,
cognition and aging. Cultured cell studies showed that DHEAS may mediate its action by counteracting aging-associated inflammation
via PPAR-α activation. In the present study, we demonstrated an age-dependent increase in IL-1β and TNF-α expression in the
brain and the spleen of aging rats, while PPAR-α expression was decreased in the spleen of 18 month-old rats. Oral treatment
with DHEAS increased PPAR-α mRNA in 3 month-old rats and decreased PPAR-α protein expression in 18 month-old rats in the spleen.
In contrast, DHEAS did not alter cytokine expression in spleen and brain of the three age groups. These findings underline
a differential role for DHEAS in PPAR-α expression that is age-dependent, and also, that beneficial effects of DHEAS on cognitive
function are unlikely mediated by a decrease in cytokine expression. 相似文献
6.
Toshihiro Fujimoto Michael A. O’Donnell Akos Szilvasi H. Yang R. B. Duda 《Cancer immunology, immunotherapy : CII》1996,42(5):280-284
Although immunotherapy with bacillus Calmette Guérin (BCG) is an established adjuvant treatment for malignant melanoma, the
mechanism of its role in this process is unclear. To investigate the possible contribution of tumor-inhibitory cytokines induced
by BCG, B16F10 melanoma cell growth in culture was assessed in response to purified cytokines and conditioned media of BCG-stimulated
splenocytes. Interferon-γ (IFNγ) was the most potent single agent (IC50≈50 pg/ml). Tumor necrosis factor α was substantially weaker (IC50>10 ng/ml) but provided synergy with IFNγ. None of the other
cytokines such as interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-12, or granulocyte/macrophage-colony-stimulating factor had
direct antitumor activity against B16F10 melanoma cells. However, when IL-2 and/or GM-CSF were combined with BCG either by
exogenous addition or through endogenous production by novel cytokine-secreting recombinant BCG (rBCG), a substantial increase
in INFγ production by splenocytes was observed. Antitumor activity of this conditioned medium directly correlated with IFNγ
concentration and was completely blocked by neutralizing antibody to IFNγ. These results suggest that BCG may exert part of
its antitumor action on melanoma through the induction of IFNγ, which can be greatly enhanced through the concomitant addition
of IL-2 and/or GM-CSF. Furthermore, by utilizing rBCG that secrete these cytokines, it may be possible to potentiate the antitumor
effect of BCG directly at the site of BCG inoculation.
Received: 29 January 1996 / Accepted: 9 April 1996 相似文献
7.
Synergy between interleukin-2 and prothymosin α for the increased generation of cytotoxic T lymphocytes against autologous human carcinomas 总被引:3,自引:0,他引:3
Voutsas IF Baxevanis CN Gritzapis AD Missitzis I Stathopoulos GP Archodakis G Banis C Voelter W Papamichail M 《Cancer immunology, immunotherapy : CII》2000,49(8):449-458
Peripheral blood mononuclear cells (PBMC) from cancer patients were cultured in vitro with irradiated autologous tumor cells
isolated from malignant effusions (mixed lymphocyte tumor cultures, MLTC) and low-dose (50 IU/ml) recombinant interleukin-2
(IL-2). The combination of IL-2 and prothymosin α (ProTα) resulted in a greater PBMC-induced response to the autologous tumor
than that brought about by IL-2 alone. In particular, ProTα specifically enhanced the CD4+ T-cell-mediated proliferation against the autologous tumor. CD4+ T cells seemed to recognize tumor antigens presented by HLA-DR molecules expressed on the autologous monocytes, since preincubation
of the latter with an anti-HLA-DR monoclonal antibody (mAb) abrogated the response. In addition, MLTC set up with IL-2 and
ProTα also generated more MHC-class-I-restricted cytotoxic T lymphocytes (CTL) against the autologous tumor than did MLTC
set up with IL-2 alone. The MLTC-induced CTL contained high levels of cytoplasmic perforin and their development was strictly
dependent on the presence of both autologous CD4+ T cells and monocytes. In the absence of either population there was a strong impairment of both proliferative and cytotoxic
responses which was not restored by the presence of ProTα. In contrast, when both cell populations were present, ProTα exerted
optimal enhancement of CD4+ T cell proliferation, which was associated with potentiated CTL responses. Our data emphasize the role of ProTα for the enhancement
of IL-2-induced CTL responses against autologous tumor cells. Such responses require collaborative interactions between CD4+, CD8+ T cells and monocytes as antigen-presenting cells. Our data are relevant for adoptive immunotherapeutic settings utilizing
IL-2 and ProTα-induced autologous-tumor-specific CTL.
Received: 2 March 2000 / Accepted: 1 June 2000 相似文献
8.
Tomohiro Yamaguchi Youichi Suzuki Ryuichi Katakura Takusaburo Ebina Junkichi Yokoyama Yoshiaki Fujimiya 《Cancer immunology, immunotherapy : CII》1998,47(2):97-103
γδT cells play a regulatory role in both primary and metastatic tumor growth in humans. The mechanisms responsible for the
activation and proliferation of circulating γδT cells should be fully understood prior to their adoptive transfer to cancer
patients. We have examined in vitro functional effects of interleukin-15 (IL-15) on highly purified γδT cells isolated from
glioblastoma patients. γδT cells constitutively express the heterotrimeric IL-2 receptor (IL-2R) αβγ, but the levels of IL-2Rβ
or γ expression were not increased by incubation with saturating amounts of IL-15. IL-15 was shown to induce a maximal γδT
cell proliferation, although at much higher concentrations (at least 2000 U/ml) than IL-2 (100 U/ml). Submaximal concentrations
of IL-15 plus low concentrations of IL-2 produced an additive proliferative response. In contrast to the IL-2-induced response,
this activity was completely or partially abrogated by anti-IL-2Rβ, or anti-IL-2Rγ antibodies, but not by anti-IL-2Rα antibodies.
Incubation of γδT cells in the presence of IL-15 resulted not only in the appearance of NK and LAK activity, but also in specific
autologous tumor cell killing activity, an additive effect being seen with IL-15 and IL-2. This IL-15-induced tumor-specific
activity could be significantly blocked by anti-IL-2Rγ and anti-IL-2R-β mAb, but not by anti-IL-2Rα mAb. Thus, in contrast
to IL-2, IL-15 activates tumor-specific γδT cells through the components of IL-2Rβ and IL-2Rγ, but not IL-2Rα. These enhanced
in vitro tumor-specific and proliferative responses of γδT cells seen with IL-15 suggest a rational adjuvant imunotherapeutic
use of γδT cells in cancer patients.
Received: 23 January 1998 / Accepted: 20 May 1998 相似文献
9.
This study examined the interaction of the poorly metastatic human melanoma cell line M4Be and the highly metastatic clone
4 derived from M4Be, with respect to fresh adherent leukocytes (AL) isolated from 17 different healthy blood donors. These
AL contained 80% (73%–93%) monocytes, 15% (6%–20%) B lymphocytes and 5% (1%–8%) T lymphocytes. The survival of these tumor
cells against the stress exerted by these AL was estimated with a clonogenic assay where isolated tumor cells were co-cultured
for 14 days in contact with AL and lipopolysaccharide (LPS). For a given blood donor, AL either stimulates or inhibits the
colony formation of the tumor cells (T) depending on the AL/T ratio, the AL activation status and the metastatic potential
of tumor cells. At low AL/T ratios (<10/1) in the presence of low (8 ng/ml) and trace (8 pg/ml) levels of LPS, hydrogen peroxide
(H2O2) release is significantly reduced, and tumor cells significantly increase their colony formation; the feeder effect of AL
is suggested to be due to low concentrations of soluble tumor necrosis factor-alpha (TNF-α). At high AL/T ratios (>10/1),
whatever the characteristics of the blood donor, clone 4 is significantly more sensitive than M4Be to AL activated with medium
containing low (8 ng/ml) or high (1,000 ng/ml) levels of LPS; this killing effect is suggested to be due to TNF-α, both soluble
and membrane-bound, but not to be due to release of H2O2. These data suggest that the regulatory role of AL, which remove the majority of human melanoma cells and stimulate the colony
formation of a small fraction of them, is partly due to TNF-α.
Received: 2 November 2000 / Accepted: 15 February 2001 相似文献
10.
Stimulating or modulating the release of cytokines by immunomodulators or immunostimulating agents is an attractive mode for treating several diseases such as viral infections. For instance, patients with viral infections may be in need of increasing or inducing T helper 1 (Th1) or proinflammatory cytokines, which ultimately activate T cytotoxic and Natural killer lymphocytes to kill virally infected cells. Of these agents, we found that Eriobotrya japonica hydrophilic leaf extract (EJHE) can induce and modulate cytokines in dose-dependent manner. Twenty-four hour exposure of increasing concentrations of EJHE increased significantly (p < 0.001) the production of IFN-γ and TNF-α, from PHA+LPS-stimulated whole blood. However, the production of IFN-γ and TNF-α plateaued at high EJHE concentrations (10–100 μg/ml). No significant changes in the production of IL-10 were seen. In addition, EJHE at 1 and 10 μg/ml reversed significantly (p < 0.01) the inhibitory effect of hydrocortisone on the IL-12 p70, IFN-γ and TNF-α production from PHAS+LPS stimulated whole blood. Without PHA and LPS, EJHE was found to induce significantly (p < 0.001) IFN-γ, IL-12 p70, TNF-α, and IL-10 from whole blood culture in concentration dependent manner. The maximum induction of IFN-γ, IL-12 p70, and TNF-α by EJHE was at 1 and 10 μg/ml. On the other hand, IL-10 induction kept increasing even at the highest concentration used (100 μg/ml) of EJHE. Furthermore, intra-peritoneal injection of EJHE into mice increased significantly serum cytokines level mainly at 10 and 100 μg/ml. Two-hour post i.p. injection, EJHE increased serum IFN-γ, TNF-α, and IL-10 to 750, 1000, and 250 pg/ml, respectively. However, 24 h post i.p. injection, the levels of TNF-α, and IL-10 were similar to basal levels but IFN-γ levels were 200 pg/ml. These results indicate that EJHE induces proinflammatory and Th1 cytokines in concentration dependent manner and the effect of this induction should be studied further in viral models to check the efficacy of such cytokine induction. 相似文献
11.
Kazuo Fushimi Kakuji Torigoe Hiroshi Yamauchi Shouji Furusako Masashi Kurimoto Masayoshi Namba 《In vitro cellular & developmental biology. Animal》1998,34(6):463-467
Summary To develop a new gene therapy model for cancer, a clonal cell line (KMST-6/TNF) which produces human tumor necrosis factor
α (hTNF-α) has been developed by introducing hTNF-α cDNA into a human immortal fibroblast cell line (KMST-6). The conditioned
medium (CM) of KMST-6/TNF cells inhibited the growth of various malignant human cell lines, but not that of normal human fibroblasts.
Although the growth inhibitory effects of KMST-6/TNF CM were neutralized to a considerable degree by anti-TNF-α antibody,
its inhibitory effects were more marked than the purified human natural TNF-α itself in the same units, suggesting that KMST-6/TNF
CM contains some growth inhibitory substances other than TNF-α. However, interferons α, β, and γ were undetectable in the
KMST-6/TNF CM. 相似文献
12.
Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin 总被引:6,自引:0,他引:6
William B. Weglicki Terry M. Phillips Anthony M. Freedman Marie M. Cassidy Benjamin F. Dickens 《Molecular and cellular biochemistry》1992,110(2):169-173
Summary We have developed two rodent models of diet-induced magnesium-deficiency in which histologically defined cardiac lesions can
be induced within two to three weeks. During the development of these lesions, the magnesium-deficient animals exhibit circulating
cytokine levels which are indicative of a generalized inflammatory state. Dramatic elevations of the macrophage-derived cytokines,
IL-1, IL-6, and TNF-α together with signigicantly elevated levels of the endothelial cell-derived cytokine, endothelin, were
detected in the plasma of these animals. We believe that the pathophysiological effects caused by the action of these cytokines
may play a role in the promotion of cardiovascular pathology associated with magnesium deficiency. 相似文献
13.
Wei-Dong Yu Ming-Jei Chang Donald L. Trump C. S. Johnson 《Cancer immunology, immunotherapy : CII》1997,44(6):316-322
Interleukin-1α (IL-1α) has potent acute antitumor activity in vivo and can enhance the efficacy of chemotherapeutic drug-mediated
antitumor responses. Studies were undertaken to examine the ability of IL-1α to enhance the activity of cyclophosphamide (CTX)
administered in combination with carboplatin. To determine the in vivo effect of IL-1α, CTX and/or carboplatin, mice bearing
14-day RIF-1 tumors were treated on day 0 with a concurrent i.p. injection of varying doses of CTX (5–150 mg/kg), human IL-1α
(125 μg/kg), and carboplatin (50 mg/kg) and examined 24 h later for the surviving fraction by the in vivo excision clonogenic-tumor-cell
assay. Even at the lowest doses of CTX, IL-1α significantly enhanced the clonogenic tumor cell kill when compared to treatment
with CTX alone. When carboplatin was added to the treatment schema, significantly greater clonogenic cell killing and tumor
regrowth delay were observed as compared to any agent alone or a two-drug combination (CTX/IL-1α or CTX/carboplatin). Significant
enhancement was observed even at low doses of CTX in combination with carboplatin and IL-1α. The interaction between the three-drug
combination was found to be synergistic as determined by the median dose effect with significant dose reduction apparent for
IL-1α and CTX when used in this combination. These results demonstrate that IL-1α can synergistically enhance the antitumor
efficacy of CTX and the combination of CTX and carboplatin.
Received: 11 September 1996 / Accepted: 20 May 1997 相似文献
14.
We have previously shown that oral administration of skimmed milk(SM) fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1/SM) to DBA/1 mice inhibited the development of collagen-induced arthritis (CIA). In this study, our
aim was to examine possible mechanisms of inhibiting the development of CIA. We studied the effect of OLL1073R-1/SM on cytokine
secretion from cells of popliteal lymph nodes (lymph node cells; LNC) of mice. The results showed that feeding OLL1073R-1/SM
inhibited secretion of proinflammatory cytokines such as interferon γ (IFN-γ), interleukin 6 (IL-6), tumor necrosis factor
α (TNF-α) and the chemokine, monocyte chemoattractant protein 1 (MCP-1). The most prominent effect was inhibition of TNF-α.
Secretion of IL-2 and IL-4 were not influenced. Feeding OLL1073R-1/SM inhibited secretion of proinflammatory cytokines produced
by accessory cells, but not T cells. We conclude that CIA may be prevented via down regulation of secretion of proinflammatory
cytokines such as IL-6, TNF-α and IFN-γ, and of the chemokine of MCP-1.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
15.
Some endotoxic properties of lipopolysaccharides (LPS) and lipids A (LA) from the marine bacteria Marinomonas communis ATCC 27118T, Marinomonas mediterranea ATCC 700492T, and Chryseobacterium indoltheticum CIP 103168T were studied. The preparations tested were shown to have high 50% lethal doses (4 μg per mouse for LPS from M. mediterranea and more than 12 μg per mouse for two other LPS and LA from C. indoltheticum) and were moderate (371 ± 37 pg/ml at 10 μg/ml of C. indoltheticum LPS), weak (148 ± 5 pg/ml at 1 μg/ml of M. mediterranea LPS), and zero (LA and LPS from M. communis and LA from C. indoltheticum) inducers of tumor necrosis factor α (TNF-α) release from peripheral human blood cells. The capacity of the LA and LPS samples
from marine bacteria to inhibit TNF-α release induced by LPS from Escherichia coli O55: B5 (10 ng/ml) was also studied.
Published in Russian in Biokhimiya, 2006, Vol. 71, No. 7, pp. 936–944. 相似文献
16.
Peroxisome proliferator-activated receptor gamma (PPARγ) activation by its ligands reportedly inhibits monocyte function.
However, because the concentrations of PPARγ ligands used in previous studies were higher than typically expected to activate
PPARγ, we clarified whether PPARγ ligands influence monocyte function and cell viability of the human monocyte cell line THP-1.
We determined tumor necrosis factor-alpha (TNF-α) release as a monocyte function and cell viability using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
bromide. Both troglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15-d-PGJ2) seemed to inhibit phorbol ester-induced TNF-α release from THP-1 cells. On the other hand, neither pioglitazone
nor rosiglitazone inhibited phorbol ester-induced TNF-α release. Because the cytotoxicity of troglitazone and 15-d-PGJ2 was
significantly (p<0.05, Tukey–Kramer) stronger than that of pioglitazone and rosiglitazone, the inhibition of TNF-α release seemed to parallel
the lack of cell viability. We concluded that PPARγ ligands did not directly inhibit TNF-α release in THP-1 cells.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
17.
Birk Poller Jürgen Drewe Stephan Krähenbühl Jörg Huwyler Heike Gutmann 《Cellular and molecular neurobiology》2010,30(1):63-70
Brain capillary endothelial cells form the blood–brain barrier (BBB), a highly selective permeability membrane between the
blood and the brain. Besides tight junctions that prevent small hydrophilic compounds from passive diffusion into the brain
tissue, the endothelial cells express different families of drug efflux transport proteins that limit the amount of substances
penetrating the brain. Two prominent efflux transporters are the breast cancer resistance protein and P-glycoprotein (P-gp).
During inflammatory reactions, which can be associated with an altered BBB, pro-inflammatory cytokines are present in the
systemic circulation. We, therefore, investigated the effect of the pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6
(IL-6) and tumor necrosis factor-α (TNF-α) on the expression and activity of BCRP and P-gp in the human hCMEC/D3 cell line.
BCRP mRNA levels were significantly reduced by IL-1β, IL-6 and TNF-α. The strongest BCRP suppression at the protein level
was observed after IL-1β treatment. IL-1β, IL-6 and TNF-α also significantly reduced the BCRP activity as assessed by mitoxantrone
uptake experiments. P-gp mRNA levels were slightly reduced by IL-6, but significantly increased after TNF-α treatment. TNF-α
also increased protein expression of P-gp but the uptake of the P-gp substrate rhodamine 123 was not affected by any of the
cytokines. This in vitro study indicates that expression levels and activity of BCRP, and P-gp at the BBB may be altered by
acute inflammation, possibly affecting the penetration of their substrates into the brain. 相似文献
18.
Michael Hoffmann Mathias Schmidt Winfried Wels 《Cancer immunology, immunotherapy : CII》1998,47(3):167-175
Tumor necrosis factor (TNF)-α has a broad range of biological activities, which depend heavily on cell type and physiological
condition. In a panel of human tumor cell lines we analyzed expression of the receptor tyrosine kinases EGFR, ErbB2 and ErbB3,
and the response to TNF-α. Among the cell lines tested those resistant to TNF-α were found to express high levels of either
EGFR, or ErbB2 and ErbB3. In TNF-sensitive breast and cervical carcinoma cells activation of EGFR or ErbB2 by the exogenous
growth factors EGF and heregulin β1 resulted in a significant increase in the number of cells surviving TNF-α treatment. In
contrast, inhibition of EGFR activation in TNF-resistant breast carcinoma cells by the novel antagonistic anti-EGFR antibody
14E1 sensitized the cells to the cytotoxic effects of TNF-α. A bacterially expressed fusion protein consisting of a 14E1 single-chain
(sc) Fv antibody fragment linked to human TNF-α retained TNF-α activity. This scFv(14E1)-TNF-α molecule localized specifically
to EGFR on the surface of tumor cells and activated the NF-κB pathway in co-cultured T cells, as demonstrated by electrophoretic
mobility shift assays.
Received: 6 May 1998 / Accepted: 16 July 1998 相似文献
19.
IFN-α regulates IL 10 production by CML cells in vitro 总被引:1,自引:0,他引:1
Graham Pawelec Elke Schlotz Arnika Rehbein 《Cancer immunology, immunotherapy : CII》1999,48(8):430-434
High levels of spontaneous in vitro IL 10 secretion by a subset of untreated chronic phase CML patients' cells are shown
to be decreased in the presence of IFN-α. However, the lower level of spontaneous IL 10 secretion by healthy control cells
are was not depressed by IFN-α. In contrast to its effects on IL 10 production, IFN-α increased the low spontaneous secretion
of IL 1α by patients' cells, bud did not further increase the higher levels of spontaneous IL 1β secretion by normal cells.
It had no effect on secretion of TNF-α by patients or normals. Spontaneous secretion of IL-1α (or IFN-γ) by patients' cells
was not observed whether or not IFN-α was present. Therefore, one mechanism of action of IFN-α in vivo may involve decreasing
endogenous IL 10 secretion (thereby reducing suppressive effects on T cell reactivity) and increasing IL 1β secretion (thereby
enhancing antigen presentation).
Received: November 1998 / Accepted: 1 March 1999 相似文献
20.
T cell clones (CD4+CD8–TCRαβ+γδ–) derived from bone marrow transplant recipients were stimulated with phytohaemagglutinin (PHA) +interleukin-2 (IL-2) in the
presence of irradiated (50 Gy) peripheral blood mononuclear cells (PBMC) derived from acute leukaemia patients(leukaemic PBMC
containing more than 95% blast cells). Leukaemic PBMC could function as accessory cells during mitogenic T cell activation
resulting in both T cell proliferation and a broad T cell cytokine response [IL-3, IL-4, IL-10, granulocyte/macrophage-colony-stimulating
factor (GM-CSF) tumour necrosis factor α (TNFα) and interferon γ (IFNγ) secretion]. Blockade of IL-1 effects by adding IL-1
receptor antagonist together with PHA+IL-2+leukaemia blasts increased T cell proliferation, whereas IL-6-neutralizing antibodies
did not alter T cell proliferation. A qualitatively similar T cell cytokine response and a similar cytokine profile (highest
levels detected for GM-CSF and IFNγ) were detected when normal polyclonal T cell lines were stimulated with PHA in the presence
of non-irradiated leukaemic PBMC. When leukaemic PBMC derived from 18 acute myelogenous leukaemia patients were cultured with
PHA and cells from a polyclonal T cell line, increased concentrations of the T cell cytokines IFNγ and IL-4 were detected
for all patients. We conclude that T cell activation resulting in proliferation and a broad cytokine response can take place
in the presence of excess acute myelogenous leukaemia blasts.
Received: 30 November 1995 / Accepted: 9 January 1996 相似文献