共查询到10条相似文献,搜索用时 156 毫秒
1.
S. J. D. Vitkus S. A. Hanifin D. W. McGee 《In vitro cellular & developmental biology. Animal》1998,34(8):660-664
Summary Intestinal epithelial cells (IEC) have previously been shown to produce several cytokines including interleukin-6 (IL-6).
However, many factors which may regulate IL-6 secretion by human IEC still remain a mystery due in part to the lack of appropriate
model cell lines and the difficulty of culturing human IEC over long periods of time. We have determined that the human colonic
carcinoma cell line Caco-2 is capable of secreting IL-6 when stimulated by the inflammatory cytokines IL-1β or tumor necrosis
factor-α (TNF-α), and stimulation of these cells with IL-1β plus TNF-α induced a synergistic enhancement of IL-6 secretion.
The inflammatory cytokine-induced enhancement in IL-6 secretion was greatest when the cells were cultured in a 10% CO2 atmosphere as compared to cells grown in 5% CO2, suggesting that environmental CO2 levels may affect IEC cytokine secretion. Finally, long-term culture of the Caco-2 cells to induce cellular differentiation
had no effect on the capacity of these cells to produce IL-6, indicating that the regulation of IL-6 secretion was not affected
by differentiation. Taken together, these studies provide important information on the factors which regulate IL-6 secretion
by human IEC as they may contribute to the cytokine network during a mucosal inflammation. The results also suggest that the
Caco-2 cell line is an appropriate model for further studies on the regulation of cytokine secretion by human IEC. 相似文献
2.
Inhibition of TRAIL-induced apoptosis by IL-8 is mediated by the p38-MAPK pathway in OVCAR3 cells 总被引:2,自引:0,他引:2
Abdollahi T Robertson NM Abdollahi A Litwack G 《Apoptosis : an international journal on programmed cell death》2005,10(6):1383-1393
Introduction: TRAIL (TNF-Related Apoptosis Inducing Ligand) is a member of the TNF superfamily of cell death inducing ligands. Interestingly,
while malignant cells are responsive to TRAIL-induced cell death when used alone or in combination with other agents, normal
cells do not appear to be sensitive to this ligand, making it a desirable therapeutic compound against many cancers, including
many ovarian carcinomas. Interleukin-8 (IL-8), a member of the C-X-C chemokine family, has been found to be at significantly
higher level in the ascites from patients with ovarian cancer. We have previously demonstrated a role for IL-8 in blocking
TRAIL's ability to induce apoptosis in the ovarian cancer cell line, OVCAR3, possibly by repressing the DR4 TRAIL receptor
expression and blocking caspase-8 cleavage. In addition, we showed a member of the mitogen-activated protein kinase (MAPK)
superfamily, p38γ, is among the genes regulated in OVCAR3 cells by TRAIL and IL-8. The present study further investigates
involvement of the p38 MAPK pathway in IL-8's ability to block TRAIL-induced apoptosis in the ovarian surface epithelial cancer
cell line, OVCAR3.
Results: In this study we demonstrate that p38γ as well as p38α play a significant role in IL-8's ability to block TRAIL-induced
apoptosis. Through array analysis, as well as confirmation with other methods, we detected regulation of p38γ and p38α following
treatment of the cancer cell line with IL-8 or TRAIL. We also tested two other isoforms of p38 MAPK, p38β and p38δ, but did
not find significant regulation by IL-8 or TRAIL. We also examined activation of the p38 MAPK pathway, up-stream as well as
down-stream, and noticed activation of the pathway following treatment with TRAIL and decreased activity when IL-8 was introduced.
With the use of specific inhibitors, we were able to further confirm the role of this pathway in TRAIL-induced apoptosis,
and IL-8's ability to block this apoptosis, in ovarian cancer cell lines.
Conclusion: Taken together, these results further solidify the role of IL-8 in blocking the TRAIL-induced apoptosis in these ovarian
carcinoma cells and provide new molecular insight into this potentially important therapeutic target. 相似文献
3.
β-1,4-galactosyltransferase I (β-1,4-GalT I) plays an important role in the synthesis of the backbone structure of adhesion molecules involved in leukocyte–endothelial
cell interaction. The expression of β-1,4-GalT I mRNA increased in primary human endothelial cells after exposure to tumor necrosis factor-α (TNF-α). In the central nervous system (CNS), astrocytes play a pivotal role in immunity as immunocompetent cells by secreting
cytokines and inflammatory mediators, there are two types of astrocytes. Type-1 astrocytes can secrete TNF-α when stimulated
with Lipopolysaccharide (LPS), while the responses of type-2 astrocytes during inflammation are unknown. So we examined the
expression change of β-1,4-GalT I mRNA in type-2 astrocytes after exposure to TNF-α and LPS. Real-time PCR showed that TNF-α or LPS affected β-1,4-GalT I mRNA expression in a time- and dose-dependent manner. RT-PCR analysis revealed that TNFR1 and TNFR2 were present
in normal untreated type-2 astrocytes, and that TNF-α, TNFR1 and TNFR2 increased in type-2 astrocytes after exposure to TNF-α or LPS. Immunocytochemistry showed that TNFR1 was
expressed in the cytoplasm, nucleus and processes of normal untreated type-2 astrocytes, and distributed mainly in the cytoplasm
and processes after exposure to LPS. TNFR2 was mainly expressed in the nucleus of normal untreated type-2 astrocytes, and
distributed mainly in the processes of type-2 astrocytes after exposure to LPS. Both anti-TNFR1 and anti-TNFR2 antibodies
suppressed β-1,4-GalT I mRNA expression induced by TNF-α or LPS. From these results, we conclude that TNF-α signaling via both TNFR1 and TNFR2 translocated from nucleus to cytoplasm or processes is sufficient to induce β-1,4-GalT I mRNA. In addition, we observed that not only exogenous TNF-α but also TNF-α produced by type-2 astrocytes affected β-1,4-GalT I mRNA production in type-2 astrocytes. These results suggest that an autocrine loop involving TNF-α contributes
to the production of β-1,4-GalT I mRNA in response to inflammation.
Chunlin Xia is the co-first author. 相似文献
4.
Plasma essential trace elements, selenium, copper, zinc, and iron concentrations and the levels of immunoregulatory cytokines,
interleukin-1β (IL-1β), interleukin-2 receptor (IL-2r), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) were evaluated in patients with cutaneous leishmaniasis (CL) to investigate a possible role of these cytokines on selenium,
zinc, copper, and iron homeostasis in CL patients. Plasma albumin levels were measured as an index of nutritional status.
Plasma selenium, zinc, and iron concentrations, and IL-2r levels were significantly lower, and copper concentrations and IL-1β, IL-8, IL-6 and TNF-α levels were significantly higher in patients with CL than those of healthy controls. There was no significant difference
in plasma albumin levels between two groups. There were positive important correlations between plasma selenium and IL-2r,
copper and IL-6, and copper and IL-1β, and negative correlations between selenium and IL-8, iron and TNF-α, and zinc and IL-1β contents in patients with CL. Our results showed that plasma trace element contents change in patients with CL. These changes
may not be a result of a specific deficiency from dietary inadequacies or imbalances, but, probably, a result of a part of
the defense strategies of an organism that is regulated by immunoregulatory cytokines. 相似文献
5.
Up-regulation of E-cadherin and β-catenin in human hepatocellular carcinoma cell lines by sodium butyrate and interferon-α 总被引:1,自引:0,他引:1
Masuda T Saito H Kaneko F Atsukawa K Morita M Inagaki H Kumagai N Tsuchimoto K Ishii AH 《In vitro cellular & developmental biology. Animal》2000,36(6):387-394
Summary Human E-cadherin is a homophilic cell adhesion molecule and its expression is well preserved in normal human hepatocytes;
a decrease in its expression has been observed in poorly differentiated hepatocellular carcinoma cells. We examined the alteration
of E-cadherin and catenin expressions caused by differentiation inducers in human hepatocellular carcinoma cells. Hepatocellular
carcinoma cell lines, HCC-T and HCC-M, were cultured with all-trans retinoic acid (ATRA), dexamethasone (DEX), sodium butyrate, and interferon-α. E-cadherin expression was only up-regulated
by butyrate and interferon-α (IFN-α) in both cell lines, studied by means of fluorescence immunostaining and flow cytometry.
The localization of E-cadherin staining was shown at their cell membrane. According to the increase in E-cadherin expression,
β-catenin expression appeared at the cell membrane of both cell lines when treated with butyrate and IFN-α. Such an appearance
was not observed when cells were treated with ATRA and DEX. Western blotting showed that α-and γ-catenin expression was not
changed, while only the expression of β-catenin increased. β-Catenin oncogenic activation as a result of amino acid substitutions
or interstitial deletions within or including parts of exon 3, which has been demonstrated recently, was not detected in these
cell lines by direct deoxyribonucleic acid sequencing. These results suggest that the expression and interaction between E-cadherin
and wild-type β-catenin are potentially modulated by butyrate and IFN-α, and that these two agents are potent inhibitors of
hepatocellular carcinoma cell invasion and metastasis. 相似文献
6.
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
7.
Summary. The effect of taurine (Tau) and taurine chloramine (Tau-Cl) on the production of TNF-α, IL-1β, and IL-6 by peripheral blood mononuclear cells of healthy volunteers was examined. Cells were stimulated with bacterial
lipopolysaccharide (LPS) in the presence of either Tau or Tau-Cl. After 24 h culture the cytokine concentrations were measured
in both culture supernatants (secreted) and cell lysates (cell-associated) using ELISA. In LPS-stimulated cells Tau-Cl inhibited
both the secreted and cell-associated IL-1β and IL-6, while exerted dual effect on TNF-α production: raising it slightly at low and reducing at higher concentration. By contrast, Tau had no significant effect on
the cytokine production. These results indicate that Tau-Cl modulates synthesis of pro-inflammatory cytokines, and therefore
it may play a role in the initiation and propagation of immune response.
Received November 29, 2001 Accepted January 18, 2002 Published online August 30, 2002
Acknowledgments This research was supported by grants from the State Committee for Scientific Research of Poland (No 4 P05B 01018) and the
Institute of Rheumatology (No I/14). The Institute of Rheumatology is supported by a core grant from the State Committee for
Scientific Research of Poland.
Authors' address: Ewa Kontny, Ph.D., Department of Pathophysiology and Immunology, Institute of Rheumatology, Spartanska 1, 02-637 Warsaw,
Poland, E-mail: zpatiir@warman.com.pl
Abbreviations: Tau, taurine; Tau-Cl, taurine chloramine; LPS, lipopolysaccharide; TNF-α, tumor necrosis factor-α; IL-1β, interleukin 1β; IL-6, interleukin 6; PBMC, peripheral blood mononuclear cells 相似文献
8.
Immunostimulating activity by polysaccharides isolated from fruiting body of <Emphasis Type="Italic">Inonotus obliquus</Emphasis> 总被引:1,自引:0,他引:1
In this study, we investigated the immunostimulating activity of polysaccharides isolated from fruiting body of Inonotus obliquus (PFIO). Additionally, the signaling pathway of PFIO-mediated macrophage activation was investigated in RAW264.7 macrophage
cells. We found that PFIO was capable of promoting NO/ROS production, TNF-α secretion and phagocytic uptake in macrophages, as well as cell proliferation, comitogenic effect and IFN-γ/IL-4 secretion in mouse splenocytes. PFIO was able to induce the phosphorylation of three MAPKs as well as the nuclear translocation
of NF-κB, resulting in activation of RAW264.7 macrophages. PFIO also induced the inhibition of TNF-α secretion by anti-TLR2 mAb, consequently, PFIO might be involved in TNF-α secretion via the TLR2 receptor. In addition, our results showed that oral administration of PFIO suppressed in vivo growth of melanoma tumor in tumorbearing mice. In conclusion, our experiments presented that PFIO effectively promotes macrophage
activation through the MAPK and NF-κB signaling pathways, suggesting that PFIO may potentially regulate the immune response. 相似文献
9.
Albena Alexandrova Elena Bandžuchová Anton Kebis Marián Kukan Daniel Kuba 《Biologia》2007,62(3):365-369
Copper is known to induce oxidative stress in a number of models. It was shown that many pathophysiological events were associated
with oxidative stress. Further, oxidative stress can increase gene expression of cytokines and of metalloproteinases. We previously
found that copper toxic effects in isolated perfused rat livers were associated with significant oxidative stress (as assessed
by lipid peroxidation, protein oxidation and oxidative DNA damage, particularly at concentration of 0.03 mM of Cu2+ in the perfusate). Here we investigated gene expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10); matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in frozen liver tissue
samples by the real-time PCR assay. Compared to controls, copper at concentration of 0.01 mM did not affect gene expression
of TNF-α, IL-10, MMP-2 and MMP-9, whereas copper at concentration of 0.03 mM significantly decreased gene expression of all the four
TNF-α, IL-10, MMP-2 and MMP-9 by 69%, 81%, 43%, and 62%, respectively. These results suggest that copper-induced oxidative stress
in the isolated rat liver can lead to the suppression of gene expression. Because TNF-α and metalloproteinases are involved also in liver regeneration, the suppression of these genes by copper may be one of the
mechanisms by which acute intoxication of animals and humans with copper may impair regenerative capability of the liver. 相似文献
10.
Méndez-Tovar LJ Mondragón-González R Vega-López F Dockrell HM Hay R López-Martínez R Manzano-Gayosso P Hernández-Hernández F Padilla-Desgarennes C Bonifaz A 《Mycopathologia》2004,158(4):407-414
IFN-γ, TNF-α, IL-4, IL10 and IL-12 concentrations in the supernatant of peripheral blood mononuclear cell (PBMC) cultures and the
in vitro proliferation of PBMC were studied in 25 patients with actinomycetoma caused by Nocardia brasiliensisand in 10 healthy controls from endemic zones. Cell cultures were stimulated by a N. brasiliensiscrude cytoplasmic antigen (NB) and five semi-purified protein fractions (NB2, NB4, NB6, NB8, and NB10) separated by isoelectric.
Phytohemagglutinin (PHA) and purified protein derivative (PPD) of Mycobacterium tuberculosiswere used as control antigens. Skin tests were performed by injecting 0.1 ml of candidin and PPD intradermally (ID). Patients
showed a poor response to tuberculin, while their response to candidin was more than two fold greater than that observed in
the controls. Cell proliferation showed no statistically significant differences in either group. IFN-γ production was higher in the healthy controls than in the patients, whereas TNF-α secretion was slightly higher in the patients’ cultures. IL-4 was detected in the patients’ cultures but not in the controls.
IL-10 and IL-12 were present at low concentrations in both groups. These results suggest that patients with actinomycetoma
show normal antigen recognition, but with low IFN-γ production, and higher concentrations of IL-4, IL-10 and TNF-α in the patients’ PBMC cultures, indicating that they probably have a Th2 type of immune response. 相似文献