共查询到20条相似文献,搜索用时 31 毫秒
1.
Tenidap is a new antiarthritic drug of novel chemical structure. This study shows the effects of tenidap on the in vitro synthesis of interleukin 1 (IL-1). IL-1 production by murine peritoneal macrophages was induced either by stimulation with lipopolysaccharide (LPS) or by phagocytosis of zymosan. With either stimulus, tenidap inhibited IL-1 production as measured by a quantitative competitive IL-1 receptor binding assay. Approximately 20 ng/mL of IL-1 was produced by 10(6) macrophages in response to LPS and about half that amount was produced in response to zymosan. Fifty percent inhibition of IL-1 production by tenidap was found at 3 microM for both stimuli. Using goat anti-IL-1 alpha and Western blot analysis, the appearance of intracellular 34 kDa pro-IL-1 alpha was inhibited by tenidap down to 3 microM. Tenidap decreased [35S]Met incorporation into cellular protein at 30 microM but not at 10 or 3 microM, indicating selectivity for IL-1 inhibition relative to total protein synthesis. Because tenidap inhibited IL-1 induction by both zymosan and LPS, it must act subsequently to receptor triggering. As the appearance of IL-1 was inhibited both intracellularly and extracellularly, the primary drug effect cannot be on secretion. 相似文献
2.
Tenidap, a new anti-inflammatory drug, is presently undergoing clinical studies as a treatment for rheumatoid arthritis (RA). Early pilot work has shown it to be of some benefit. Tenidap is a dual inhibitor of cyclo-oxygenase and 5-lipoxygenase enzymes. It has also been shown to modify white blood cell behaviour such as interleukin-1 production, monocyte differentiation and neutrophil degranulation. As free radicals (FRs) have been implicated in the pathogenesis of RA, we used an in vitro assay system developed by Misra and Fridovich to assess if tenidap has FR scavenging effects. Our study shows, for the first time, that tenidap has general FR scavenging effects although no effect on the superoxide anion (O2.-) could be demonstrated. This effect occurred in a dose-dependent manner at concentrations above 20 mug/ml (p < 0.005, Mann-Whitney U-test). As the therapeutic range of tenidap in serum is between 15 and 30 mug/ml such FR scavenging activity may be clinically relevant in the treatment of RA. Ex vivo confirmation of this possibility is underway. 相似文献
3.
4.
The cytokines IL-6, IL-1, and TNF play a key role in the pathogenesis of rheumatoid arthritis (RA) and initiate hepatic serum amyloid A (SAA) expression after injury. To provide a possible mechanistic explanation for the previous observation that plasma SAA concentrations decreased during treatment of RA patients with tenidap, but increased during treatment with naproxen, the present study compared the effects of tenidap and naproxen on the two stages of SAA expression: cytokine production by human PBMC and cytokine-stimulated SAA synthesis by human Hep3B hepatoma cells. Tenidap inhibited production of IL-6 greater than TNF greater than IL-1; the effect of naproxen on production of all three cytokines was lesser and least on IL-6. Indeed, an increase in IL-6 production was observed after exposure to naproxen. PBMC beta-2-microglobulin production and total protein synthesis were unaffected at concentrations and times at which effects on cytokine production were observed. Cell density was a significant factor in the extent to which cytokines were stimulated by LPS. Approximately physiologic cell densities, 0.5 to 1 x 10(6) cells/ml, were optimal for stimulation of IL-1-beta and IL-6 production by LPS; however, greater amounts of TNF were produced at lower cell densities. Because neither tenidap nor naproxen inhibited SAA synthesis by cytokine-stimulated Hep3B cells and because they differ most significantly in their effect on IL-6 production, the results support a role for IL-6 in the continued stimulation of SAA production during RA. 相似文献
5.
Effects of interleukin-12 on in vitro culture with interleukin-2 of regional lymph node lymphocytes from lung cancer patients 总被引:2,自引:0,他引:2
T. Hanagiri Mitsuhiro Takenoyama Takashi Yoshimatsu Chikashi Hirashima Ichiro Yoshino Kozo Nakanishi Akira Nagashima Kikuo Nomoto Kosei Yasumoto 《Cancer immunology, immunotherapy : CII》1996,43(2):87-93
In the present study, we carried out a functional analysis of regional lymph node lymphocytes (RLNL) from patients with lung
cancer after in vitro activation by interleukin-2 (IL-2) and interleukin-12 (IL-12). IL-12 (100 U/ml) enhanced both the proliferation
and cytotoxic activity of RLNL in a culture with low doses of IL-2 (5 – 10 JRU/ml). After comparing an RLNL culture with a
low dose of IL-2 alone, a higher proportion of CD8+ cells and CD56+ cells and a lower proportion of CD4+ cells were found in the culture with both IL-12 and a low dose of IL-2. Such a combination of the cytokines effectively activated
RLNL in terms of the expression of IL-2 receptors. In the culture condition of IL-12 and a low dose of IL-2, a synergistic
effect was observed in the production of such cytokines as interferon γ, tumor necrosis factor α (TNFα), and TNFβ, as well
as in tumor cytotoxicity. However, the addition of IL-12 inhibited the cytotoxicity of RLNL in the culture with a high dose
of IL-2 (100 JRU/ml). This inhibition is considered to be partially due to the endogenous production of TNFα by lymphocytes,
because the neutralization of TNFα bioactivity partially restored the cytotoxic activities of RLNL. Furthermore, in the presence
of hydrocortisone, IL-12 synergistically enhanced the cytotoxic activity of RLNL cultured with a high dose of IL-2. These
results provide useful information about the improvement of adoptive immunotherapy against cancer using RLNL.
Received: 2 February 1996 / Accepted: 30 July 1996 相似文献
6.
Takami Sato 《Cancer immunology, immunotherapy : CII》1996,43(3):174-179
We have developed a novel approach to cancer immunotherapy – an autologous whole-cell vaccine modified with the hapten dinitrophenyl
(DNP). This approach elicits significant inflammatory responses in metastatic sites and some objective tumor responses. Post-surgical
adjuvant immunotherapy with DNP-modified melanoma vaccine in a setting of micrometastatic disease produces significant survival
prolongation in stage III melanoma patients. Histologically, the inflammatory responses of the tumor consist of infiltration
by lymphocytes, the majority of which are CD8+, HLA-DR+ T cells. T cells from these lesions tend to have mRNA for interferon γ. T cell receptor analysis suggests that the tumor-infiltrating
T cells are clonally expanded. DNP-modified vaccine also induces T cells in the peripheral blood, which respond to DNP-modified
autologous cells in a hapten-specific, MHC-restricted manner. Moreover, a T cell line generated from these lymphocytes responded
to only a single HPLC fraction of MHC-associated, DNP-modified tumor peptides. Since inflammatory responses in metastases
were not consistently associated with dramatic tumor regression, we considered the possibility of immunosuppression at the
tumor site. We found that mRNA for the anti-inflammatory cytokine, interleukin-10 (IL-10) is expressed in most metastatic
melanoma tissues and subsequently demonstrated that IL-10 protein is produced by melanoma cells. Thus the efficacy of DNP
vaccine could be further enhanced by inhibition of IL-10 production or binding. Finally, we expect these results obtained
with melanoma to be applicable to other human cancers.
Received: 6 August 1996 / Accepted: 20 September 1996 相似文献
7.
Tu H Rady PL Juelich T Tyring SK Koldzic-Zivanovic N Smith EM Hughes TK 《Cellular and molecular neurobiology》2007,27(2):161-170
1. Aim: The hypothalamic-pituitary-adrenal (HPA) axis is a mediator for interactions between the immune and neuroendocrine systems.
Pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) have
been shown to activate the HPA axis. Recently, interleukin-10, an important anti-inflammatory cytokine in the immune system,
has been shown to be expressed in the central nervous system and neuroendocrine system. Little is known, however, about IL-10’s
functions in the HPA axis.
2. Methods: The Affymetrix DNA microarray (mouse genome U74Av2 Probe Array) was conducted to determine the gene expression profile regulated
by IL-10 in cells of HPA axis origin.
3. Results: In this study, we analyzed gene expression regulated by IL-10 in cells derived from the HPA axis. The results showed that
quorums of genes are modulated by IL-10 in these neuroendocrine cells.
4. Conclusions: These findings will provide a valuable repository to aid in understanding IL-10’s functions in the HPA axis at the molecular
level. 相似文献
8.
9.
X.-L. Zhang Y. Komada Yan-Wen Zhou Tong-Xin Chen Haruko Sakai Eiichi Azuma Masaru Ido Minoru Sakurai 《Cancer immunology, immunotherapy : CII》1997,44(1):41-47
Peripheral blood lymphocytes obtained from children with acute lymphoblastic leukemia (ALL) at onset were studied for the
expression of interleukin-2 (IL-2) receptor α-chain (CD25) by two-color flow-cytometric analysis. Stimulated with anti-CD3
monoclonal antibody (mAb) alone, CD25 expression was significantly suppressed in CD4+ T cells from 27 of 48 (56.3%) cases and in CD8+ T cells from 29 of 48 (60.4%) cases. When stimulated with anti-CD3 mAb plus phorbol 12-myristate 13-acetate (PMA), CD25 expression
was clearly restored in certain cases of ALL. When PMA plus ionomycin were used for stimulation of T cells, CD25 was inducible
in a majority of cases. Interestingly CD25 expression upon anti-CD3 mAb stimulation was recovered after complete remission
had been achieved. These observations suggest the presence in ALL children at onset of an in vitro defect in the signal transduction
pathway of the T-cell-receptor/CD3 complex, resulting in inefficient CD25 expression. However, immune-staining analysis indicated
that protein kinase C was normally translocated from the cytosol fraction to the cell membrane fraction. The mobilization
of cytoplasmic free calcium is also normal.
Received: 27 March 1996 / Accepted: 23 December 1996 相似文献
10.
Activation of STAT3 by IL-6 and IL-10 in primary human macrophages is differentially modulated by suppressor of cytokine signaling 3 总被引:9,自引:0,他引:9
Niemand C Nimmesgern A Haan S Fischer P Schaper F Rossaint R Heinrich PC Müller-Newen G 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(6):3263-3272
11.
Interleukin-11 and its receptor. 总被引:3,自引:0,他引:3
Interleukin (IL)-11 is a bone marrow fibroblast derived cytokine with a wide spectrum of activities in different biological systems. It has been shown that IL-11 supports the growth of certain types of plasmacytoma and hybridoma cells, enhances antigen-specific antibody responses, synergizes with IL-3 in supporting megakaryocyte colony formation, acts synergistically with IL-3 in shortening the G0 period of early progenitors, induces the synthesis of acute phase proteins, and inhibits lipoprotein lipase activity and adipocyte differentiation. The human IL-11 gene, which is localized at 19q13.3-13.4, consists of five exons and four introns. Initial biochemical characterization has identified a 151 kDa protein as the potential IL-11 binding subunit of the receptor complex. Because of the overlapping biological activities between IL-6 and IL-11, we compared the signal transduction pathways mediated by IL-6 or IL-11 in cell lines responsive to both cytokines. Results from protein tyrosine phosphorylation and immediate response gene expression suggest that there are convergent and divergent points along the signal transduction pathways utilized by IL-6 or IL-11. The IL-6 signal transducer, gp130, appears to be involved in the IL-11 mediated signaling. Other cytokines such as leukemia inhibitory factor, oncostatin M and ciliary neurotrophic factor have also been shown to utilize gp130 as a signal transducer. The significance of growth factor sharing common biological activities and signaling pathways will be discussed. 相似文献
12.
Interleukin-10 in serous ovarian carcinoma cell lines 总被引:7,自引:1,他引:6
Berger S Siegert A Denkert C Köbel M Hauptmann S 《Cancer immunology, immunotherapy : CII》2001,50(6):328-333
Interleukin-10, one of the most potent anti-inflammatory cytokines, is expressed in ovarian carcinomas in vivo. In contrast to the high levels of IL-10 in ascites and tumour tissue, the expression of this cytokine appears to be a rare
event in ovarian carcinoma cell lines in vitro. Virtually nothing is known about the regulation of IL-10 expression in ovarian
carcinoma cell lines. We investigated the expression of IL-10 in four cell lines originally derived from ovarian serous adenocarcinoma:
OVCAR-3, SKOV-3, CAOV-3 and OAW-42. IL-10-specific mRNA was detected in OVCAR-3 and only this cell line produced IL-10 constitutively
under serum-free conditions as well as in serum-containing medium. Our studies on the regulation of IL-10 secretion in OVCAR-3
revealed that (1) proinflammatory stimuli IL-1β and TNF-α, but not LPS, enhance IL-10 secretion, (2) IL-6 has no influence on the release of IL-10, (3) prostaglandin E2 influences
neither the spontaneous nor the TNF-α- or IL-1β-stimulated IL-10 production and (4) interferon-γ inhibits IL-10 secretion. We conclude that only a minority of serous ovarian carcinoma cells maintain the ability to produce
IL-10 in vitro. Our data on the regulation of IL-10 production in OVCAR-3 indicate that ovarian carcinoma cells share some, but not all,
of the regulatory features typical for the monocytic IL-10 secretion.
Received: 1 February 2001 / Accepted: 29 March 2001 相似文献
13.
K. Vihko Marjo Seppänen Tiina Henttinen Juha Punnonen Seija Grénman Reijo Punnonen 《Cancer immunology, immunotherapy : CII》1997,43(6):368-374
The biology and pathogenesis of vulvar carcinoma are poorly understood at present. In order to understand this disease better,
we have used recently developed squamous cell carcinoma lines of the vulva as models. Two cell lines originating from two
individuals (UM-SCV-1A and UM-SCV-6) were cultured in vitro in 10% fetal calf serum. The effects of interleukins 10 and 13,
interferons α and γ, granulocyte/macrophage-growth-stimulating factor (GM-CSF), tumor necrosis factor α (TNFα), and transforming
growth factor β (TGFβ) on the proliferation of the cells was investigated by using radioactively labelled uridine as tracer.
In addition, an investigation on the molecular structure of extracted cellular DNA was carried out to investigate whether
programmed cell death (apoptosis) would be inducible by any of the factors. In UM-SCV-1A cells, interleukin-10 (IL-10) and
interleukin-13 (IL-13) caused an approximately 12-fold decrease in DNA synthesis in cells cultured for 72 h (P<0.001), while GM-CSF had no significant effect. TGFβ showed a significant inhibitory effect on deoxyuridine incorporation
(P<0.001), which was 2.0- and 4.2-fold at 48 h and 72 h, respectively. TFGα showed a 1.2-fold inhibitory effect on DNA synthesis
at 48 h (P<0.01) and a 1.5-fold inhibition at 72 h (P<0.05). Interferon γ (IFNγ) showed an inhibitory effect on DNA synthesis (1.3-fold; P<0.01). In UM-SCV-6 cells, both IL-10 and IL-13 showed inhibitory effects on deoxyuridine incorporation (1.3- and 1.4-fold
at 48 h, respectively; P<0.001) that were even more pronounced at 72 h (2.4- and 2.5-fold respectively; P<0.001). IFNγ caused a 3.6-fold inhibition of DNA synthesis by UM-SCV-6 cells at 72 h (P<0.001). Both TFGβ and TNFα inhibited uridine incorporation (3.0- and 1.6-fold at 48 h, respectively; 2.7-fold at 72 h for
both factors). GM-CSF inihibited DNA synthesis by UM-SCV-6 cells 1.3- 2.0-fold at 48 h and 72 h, respectively. In dose/response
analyses, the effect of INFα on DNA synthesis was inhibitory in both cell lines at 48 h, while stimulatory effects were observed
at 72 h. Electrophoretic analyses of DNA isolated from cells cultured in the presence or absence of different factors did
not reveal DNA fragmentation. All cytokines, with the exception of IFNα, showed inhibitory effects on DNA synthesis by vulvar
carcinoma cells. Of the factors studied, the recently described interleukins 10 and 13 showed potent inhibition of cell growth,
encouraging further investigation on the molecular mechanisms of the observed inhibition. Apoptosis does not seem to be induced
in the two vulvar carcinoma cell lines by any of the cytokines studied.
Received: 26 March 1996 / Accepted: 5 December 1996 相似文献
14.
Bernd L. Fiebich Michael Hüll Klaus Lieb Karin Gyufko Mathias Berger Joachim Bauer 《Journal of neurochemistry》1997,68(2):704-709
Abstract: Prostaglandins (PGs) and cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), have been implicated in the etiopathology of various inflammatory and degenerative disorders, including Alzheimer's disease (AD) and prion diseases. Nonsteroidal antiinflammatory drugs (NSAIDs), potent inhibitors of PG synthesis, appear to be beneficial in the treatment of AD. To assess whether PGs are able to induce IL-6 synthesis in cells of the CNS, IL-6 mRNA and protein syntheses were measured in a human astrocytoma cell line after stimulation with different PGs. PGE1 and PGE2 , but not PGD2 and PGF2α , led to a rapid and transient induction of IL-6 mRNA, followed by IL-6 protein synthesis. Furthermore, PGE2 potentiated IL-1β-induced IL-6 mRNA synthesis. These results are discussed with respect to the participation of PGs in neurodegenerative diseases (and its inhibition by NSAIDs) by affecting cytokine expression. 相似文献
15.
Molnar C Garcia-Trevijano ER Ludwiczek O Talabot D Kaser A Mato JM Fritsche G Weiss G Gabay C Avila MA Tilg H 《European cytokine network》2004,15(4):303-311
Hepatocyte growth factor (HGF) prevents liver failure in various animal models including endotoxin-induced acute liver failure. We were interested to find out whether human HGF exerts anti-inflammatory effects by modulation of cytokine synthesis. Therefore, human HepG2 cells were cultured with increasing concentrations of HGF. HGF dose-dependently upregulated the production of interleukin-1 receptor antagonist (IL-1Ra). Incubation of HepG2 cells with interleukin-1beta (IL-1beta) caused an increase in IL-1Ra levels, while interleukin-6 (IL-6) had no effect on IL-1Ra synthesis. Co-stimulation of HepG2 cells with HGF + IL-1beta resulted in a synergistic effect on IL-1Ra mRNA and protein expression. Stimulation of freshly isolated mouse hepatocytes from male C57 BL/6 mice with HGF increased IL-1Ra mRNA and protein synthesis dose-dependently. A co-stimulation with HGF and IL-1beta had a synergistic effect on IL-1Ra mRNA expression but only a partially additive effect on IL-1Ra protein synthesis. HGF-induced IL-1Ra production was significantly decreased by the mitogen-activated protein kinase (MAPK) inhibitor PD98059. Accordingly, HGF stimulation specifically increased MAPK-dependent signalling pathway (p42/44). In contrast, in preactivated PBMC mRNA expression and protein synthesis of IL-1Ra, interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) were unaffected after stimulation with HGF. In conclusion, our data suggest that HGF exerts anti-inflammatory effects by modulating the signal transduction cascade leading to increased expression of IL-1Ra, which might explain the protective and regenerative properties of this cytokine in animal models of liver failure. 相似文献
16.
17.
Qasimi P Ming-Lum A Ghanipour A Ong CJ Cox ME Ihle J Cacalano N Yoshimura A Mui AL 《The Journal of biological chemistry》2006,281(10):6316-6324
18.
Canellada A Alvarez I Berod L Gentile T 《The Journal of steroid biochemistry and molecular biology》2008,111(3-5):255-261
Regulation of the immune response is necessary to allow successful pregnancy. Asymmetric IgG antibodies are involved in fetal maintenance. We have previously demonstrated that estrogen (E2) and progesterone (P4) modulate the synthesis of asymmetric antibodies but the underlying mechanisms remain unclear. Since IL-6 and a progesterone-induced blocking factor (PIBF) were shown to regulate asymmetric antibody synthesis, in this work we analyzed whether E2 and P4 were able to modulate IL-6 signal transduction pathways and the ability of P4 to induce PIBF synthesis, in hybridoma B cells was also evaluated. We found that the IL-6 treatment induced an increase in the expression of gp130 and JAK1 by the hybridoma. E2 and P4 diminished the IL-6-induced gp130 expression in a dose-dependent manner, whereas the expression of JAK1 was not significantly affected. At 10(-6)M concentration, the steroids inhibited the phosphorylation of gp130 and diminished the IL-6-induced STAT3 phosphorylation and traslocation to the nucleus. Maximal PIBF expression was observed when the hybridoma was cultured with 10(-10)M P4, compared to the control (p<0.05). Results demonstrate two molecular mechanisms, the modulation of the IL-6R signal transduction pathway and PIBF induction, which could be involved in the immunoregulatory role of sexual steroids during pregnancy. 相似文献
19.
Hu JL Li G Zhou DX Zou YX Zhu ZS Xu RX Jiang XD Zeng YJ 《Cellular and molecular neurobiology》2009,29(1):81-85
Neuroinflammation has been implicated in the etiology of Alzheimer’s disease (AD). Many studies have suggested that C(-889)
T promoter polymorphism in one of the proinflammatory cytokine interleukin-1 (IL-1) encoding gene IL-1A may be associated
with AD pathogenesis. To determine whether the polymorphism contributes to the risk for late-onset AD (LOAD) in Chinese, we
carried out our investigation in 344 sporadic LOAD patients and 224 healthy controls. No statistical significant association
was obtained between IL-1A C(-889) T polymorphism and LOAD and no statistical difference was found between cases and controls
after stratification for apolipoprotein E allele 4 (APOE ε4) status. The results reveal that it is not likely that the IL-1A
C(-889) T polymorphism is involved in AD pathogenesis in the Chinese population. Further studies of the associations between
other IL-1A genetic polymorphisms and AD should be performed in a larger population and biologic functional analysis of IL-1A
gene is required to verify the underlying roles of IL-IA in LOAD. 相似文献
20.
The use of acetylcholinesterase inhibitors to decrease the breakdown of the neurotransmitter acetylcholine has been the main
symptomatic therapy for mild to moderate Alzheimer’s patients, though the etiology of Alzheimer’s disease remains unclear
and seems to involve multiple factors. Further evidence has indicated that some of these acetylcholinesterase inhibitors also
have non-cholinergic functions on the pathogenesis of Alzheimer’s disease including the formation and deposition of β-amyloid.
Huperzine A, a potent and reversible inhibitor of acetylcholinesterase that was initially isolated from a Chinese herb, has
been found to improve cognitive deficits in a broad range of animal models and has been used for Alzheimer’s disease treatment
in China. The novel neuroprotective effects of huperzine A might yield beneficial effects in Alzheimer’s disease therapy and
provide a potential template for the design of new selective and powerful anti-Alzheimer’s drugs. The present paper gives
an overview on the neuroprotective effects of huperzine A beyond its acetylcholinesterase inhibition. These effects include
regulating β-amyloid precursor protein metabolism, protecting against β-amyloid-mediated oxidative stress and apoptosis. The
structure–function relationship of huperzine A is also discussed. 相似文献