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1.
Campo GM Avenoso A Campo S Angela D Ferlazzo AM Calatroni A 《Molecular and cellular biochemistry》2006,292(1-2):169-178
Several reports have shown that a number of cytokines such as tumor necrosis-α (TNF-α), interferon-γ (IFN-γ), and interleukin-β (IL-1β) are capable to induce hyaluronan sinthases (HASs) mRNA expression in different cell culture types. The obvious consequence of this stimulation is a marked increment in hyaluronan (HA) production. It has been also reported that oxidative stress, by itself, may increase HA levels. The aim of this study was to evaluate how TNF-α, IFN-γ,IL−1β, and exposition to oxidative stress may modulate HAS activities in normal human skin fibroblasts. Moreover, the effects on HAS mRNA expression of the concomitant treatment with cytokines and oxidants, and the HA concentrations after treatments, were studied. TNF-α, IFN-γ, and IL-1β were added to normal or/and exposed to FeSO4 plus ascorbate fibroblast cultures and HAS1, HAS2 and HAS3 mRNA content, by PCR-real time, was assayed 3,h later. HA levels were also evaluated after 24,h incubation. The treatment of fibroblasts with cytokines up-regulated HASs gene expression and increased HA production. IL-1β induced HAS mRNA expression and HA production more efficiently than TNF-α and IFN-γ. The exposition of the fibroblasts with the oxidant system markedly increased HAS activities while slightly HA production. The concomitant treatment of cells with the cytokines and the oxidant was able to further enhance, in a dose dependent way, with synergistic effect on HAS mRNA expression. On the contrary HA levels resulted unaffected by the concomitant treatment, and resemble those obtained with the exposure to FeSO4 plus ascorbate only. This lack in HA production could be due to the deleterious action of free radicals on the HA synthesis. 相似文献
2.
To determine some early signs connected with the increased risk of future allergy development, gene expression and production
of selected cytokines were tested in children of allergic mothers and compared with newborns of healthy mothers. Expression
of IL-1β, IL-2, IL-4, IL-8, IL-10, IL-13, IFN-γ, TNF-α, TGF-β and EGF was tested in cord blood cells using real-time PCR and
production of these cytokines was evaluated in cord sera by ELISA. Gene expression of IL-2, IL-4, IL-8, IFN-γ, IL-1β, TNF-α
and TGF-β was decreased and that of IL-10, IL-13 and EGF increased in children of allergic mothers in comparison with those
of healthy mothers. Significant differences in sera of healthy and allergic groups were only in IL-10 and EGF. Different relationship
among serum cytokine levels reflects the fact that the cytokines are not produced only by blood cells. Significantly decreased
production of EGF in newborns of allergic mothers could negatively influence maturation of mucosal membranes of these children
and support thus their easier allergization. Allergic phenotype pointing to the bias to TH2 response and to possibly impaired intestine maturation was apparent already on the level of cord blood and could serve as
a predictive sign of increased allergy risk. 相似文献
3.
Miao Yin Liang Zhang Xiao-ming Sun Liu-feng Mao Jie Pan 《Molecular biology reports》2010,37(4):2049-2054
To investigate the effect of apolipoprotein E (apoE) on cytokine expression profile of the liver of young mice, quantitative
RT-PCR (qRT-PCR) assay and cytokine antibody array for multiplex analysis of 62 cytokines have been used to analyze characteristics
of expression of cytokines in the liver of 6-week-old apoE-null (apoE−/−) mice. The levels of plasma cytokines were also analyzed. The mRNA level of IL-1β, IL-2, IL-6, ICAM-1, VCAM-1, MCP-1, NF-κB
(p65), IFN-γ and IκB-α were increased significantly in apoE−/− mice comparative to wild-type (WT) mice. IL-4, IL-10 and GM-CSF, however, were slightly decreased. Compared with WT, levels
of 21 cytokines altered twofold or more in apoE−/− mice, including 10 cytokines increased and 11 decreased. Expression patterns of IL-1β, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ
and VCAM-1 showed identical trend between cytokine antibody array and qRT-PCR analysis. Moreover, levels of IL-1β, IFN-γ and
IL-6 in the plasma were elevated, while IL-4 was lightly decreased in apoE−/− mice compared to those in WT mice. These results implied that promotion of type I immune response in the liver of young apoE−/− mice due to alteration of these cytokines, and the phenotypes may be caused by the regulation of NF-κB. The inflammation
and lipid metabolism dysfunction in the liver cooperated in dysfunction of the liver in young apoE−/− mice. 相似文献
4.
Yamaji K Nabeshima S Murata M Chong Y Furusyo N Ikematsu H Hayashi J 《Cancer immunology, immunotherapy : CII》2006,55(4):394-403
Type I interferon (IFN) possesses antiviral and antitumor activities and also having an immune regulatory effect, activating
cellular immune response and upregulating several cytokines. Recent study has shown that type I IFN upregurates the dendritic
cell production of IL-15 capable of activating natural killer cells and CD8+ memory T lymphocytes. However, it is still unknown if type I IFN induces IL-15 production in non-immune cells and if type
I IFN affects IL-15 production in vivo. The present study investigated the effect of type I IFNs on IL-15 expression in hepatocellular
carcinoma (HCC) cell lines in vitro and in patients with chronic hepatitis C in vivo. When three HCC cell lines, Huh7, HepG2,
and JHH4 were cultured in vitro, IFN upregulation of IL-15 expression was observed at both the mRNA and protein levels. In
experiments using Huh7 cells, upregulation of IL-15 expression occurred within 24 h of the start of IFN stimulation, and both
IFN-α and -β dose-dependently increased IL-15 production in the range from 100 U/ml to 10,000 U/ml of concentration. IFN-β
showed stronger activity in IL-15 production induction in vitro than IFN-α. For in vivo examination, sera were obtained from
21 chronic hepatitis C patients treated with IFN and 29 healthy individuals, and the serum IL-15 level was quantified by ELISA.
The serum IL-15 level of chronic hepatitis C patients before IFN treatment was similar to that of the healthy controls and
significantly increased only during the IFN administration period. These results confirm that IFN-α/β induce IL-15 production
and also suggest that IL-15 may be associated with type I IFN-induced immune response. 相似文献
5.
Maitake D-Fraction is a polysaccharide extracted from the maitake mushroom (Grifola frondosa S.F. Gray). It is a β-glucan with a β-1,6 main chain with β-1,3 branches. Using normal C3H/Hej mice, its effects on the natural
immune system, including macrophages, dendritic cells, and natural killer (NK) cells, were investigated. NK cells attack cells
infected with pathogens such as bacteria and virus and produce cytokines, such as interferon-gamma (IFN-γ), that can modulate
natural and specific immune responses. D-Fraction was administered to the mice intraperitoneally for 3 consecutive days; spleen
cells containing macrophages and dendritic cells were then cultured and the culture supernatants were analyzed for IL-12.
At the same time, IFN-γ expression in splenic NK cells was investigated. The levels of these cytokines were increased by D-Fraction.
To elucidate NK cell activation by D-Fraction, CD69 expression on the surface of activated NK cells was examined, resulting
in an increase in CD69-positive ratio for splenic NK cells. These results indicate that D-Fraction stimulates the natural
immunity related to the activation of NK cells indirectly through IL-12 produced by macrophages and dendritic cells. Therefore,
administration of D-Fraction to healthy individuals may serve to prevent infection.
Received: August 1, 2002 / Accepted: February 10, 2003 相似文献
6.
Katarzyna Grzelkowska-Kowalczyk Wioletta Wieteska-Skrzeczyńska 《Cellular & molecular biology letters》2010,15(1):13-31
The aim of this study was to compare the effects of TNF-α, IL-1β and IFN-γ on the activation of protein kinase B (PKB), p70S6k, mitogen-activated protein kinase (MAPK) and p90
rsk
, and on IGF-I-stimulated glucose uptake and protein synthesis in mouse C2C12 myotubes. 100 nmol/l IGF-I stimulated glucose
uptake in C2C12 myotubes by 198.1% and 10 ng/ml TNF-α abolished this effect. Glucose uptake in cells differentiated in the
presence of 10 ng/ml IFN-γ increased by 167.2% but did not undergo significant further modification upon the addition of IGF-I.
IGF-I increased the rate of protein synthesis by 249.8%. Neither TNF-α nor IFN-γ influenced basal protein synthesis, but both
cytokines prevented the IGF-I effect. 10 ng/ml IL-1β did not modify either the basal or IGF-I-dependent glucose uptake and
protein synthesis. With the exception of TNF-α causing an 18% decrease in the level of PKB protein, the cellular levels of
PKB, p70S6k, p42MAPK, p44MAPK and p90
rsk
were not affected by the cytokines. IGF-I caused the phosphorylation of PKB (an approximate 8-fold increase above the basal
value after 40 min of IGF-I treatment), p42MAPK (a 2.81-fold increase after 50 min), and the activation of p70S6k and p90
rsk
, manifesting as gel mobility retardation. In cells differentiated in the presence of TNF-α or IFN-γ, this IGF-I-mediated
PKB and p70S6k phosphorylation was significantly diminished, and the increase in p42MAPK and p90
rsk
phosphorylation was prevented. The basal p42MAPK phosphorylation in C2C12 cells treated with IFN-γ was high and comparable with the activation of this kinase by IGF-I. Pretreatment
of myogenic cells with IL-1β did not modify the IGF-I-stimulated phosphorylation of PKB, p70S6k, p42MAPK and p90
rsk
. In conclusion: i) TNF-α and IFN-γ, but not IL-1β, if present in the extracellular environment during C2C12 myoblast differentiation,
prevent the stimulatory action of IGF-I on protein synthesis. ii) TNF-α- and IFN-γ-induced IGF-I resistance of protein synthesis
could be associated with the decreased phosphorylation of PKB and p70S6k. iii) The activation of glucose uptake in C2C12 myogenic cells treated with IFN-γ is PKB independent. iv) The similar effects
of TNF-α and IFN-γ on the signalling and action of IGF-I on protein synthesis in myogenic cells could suggest the involvement
of both of these cytokines in protein loss in skeletal muscle. 相似文献
7.
Judith van Holten Kris Reedquist Pascale Sattonet-Roche Tom JM Smeets Christine Plater-Zyberk Margriet J Vervoordeldonk Paul P Tak 《Arthritis research & therapy》2004,6(3):R239
We investigated the therapeutic potential and mechanism of action of IFN-β protein for the treatment of rheumatoid arthritis
(RA). Collagen-induced arthritis was induced in DBA/1 mice. At the first clinical sign of disease, mice were given daily injections
of recombinant mouse IFN-β or saline for 7 days. Disease progression was monitored by visual clinical scoring and measurement
of paw swelling. Inflammation and joint destruction were assessed histologically 8 days after the onset of arthritis. Proteoglycan
depletion was determined by safranin O staining. Expression of cytokines, receptor activator of NF-κB ligand, and c-Fos was
evaluated immunohistochemically. The IL-1-induced expression of IL-6, IL-8, and granulocyte/macrophage-colony-stimulating
factor (GM-CSF) was studied by ELISA in supernatant of RA and osteoarthritis fibroblast-like synoviocytes incubated with IFN-β.
We also examined the effect of IFN-β on NF-κB activity. IFN-β, at 0.25 μg/injection and higher, significantly reduced disease
severity in two experiments, each using 8–10 mice per treatment group. IFN-β-treated animals displayed significantly less
cartilage and bone destruction than controls, paralleled by a decreased number of positive cells of two gene products required
for osteoclastogenesis, receptor activator of NF-κB ligand and c-Fos. Tumor necrosis factor α and IL-6 expression were significantly
reduced, while IL-10 production was increased after IFN-β treatment. IFN-β reduced expression of IL-6, IL-8, and GM-CSF in
RA and osteoarthritis fibroblast-like synoviocytes, correlating with reduced NF-κB activity. The data support the view that
IFN-β is a potential therapy for RA that might help to diminish both joint inflammation and destruction by cytokine modulation. 相似文献
8.
9.
Forget MA Reuben A Turcotte S Martin J Lapointe R 《Cancer immunology, immunotherapy : CII》2011,60(8):1119-1125
Polyfunctionality is the capacity of a T-cell to execute a variety of effector functions mainly mediated by production of
cytokines, chemokines, and cytolytic enzymes. Studies in anti-viral immunity have acknowledged the importance of polyfunctionality
in the clearance of infections and maintenance of protection. Although accepted in the field, this concept has not been as
well characterized in cancer immunology. Here, we report the polyfunctionality profile analysis of a CD8+ T-cell clone isolated from a lung cancer patient and directed against Dickkopf-1, a potentially new tumor-associated antigen
(TAA). The clone showed Tc1/Th1 effector tendencies confirmed by secretion of cytokines such as IFN-γ, IP-10, MIP-1β, MIP-1α,
IL-2, GM-CSF, and expression of cytolytic enzyme granzyme B. This secretion profile is of particular interest in the context
of an anti-tumor response. Although secretion of IL-5 and IL-13 was also detected, absence of IL-4 and IL-10 opposes the idea
of cytokine-dependent Th1 inhibition. Establishing a comprehensive cytokine secretion profile may help predict T cells’ specific
response against a novel TAA in a peptide vaccination context. It may further help in selecting clones with an optimal functional
profile from the peripheral blood of cancer patients for expansion and adoptive cell transfer therapy. 相似文献
10.
Fowler DW Copier J Wilson N Dalgleish AG Bodman-Smith MD 《Cancer immunology, immunotherapy : CII》2012,61(4):535-547
Attenuated and heat-killed mycobacteria display demonstrable activity against cancer in the clinic; however, the induced immune
response is poorly characterised and potential biomarkers of response ill-defined. We investigated whether three mycobacterial
preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumour effector responses in human γδ T-cells. γδ T-cell responses were characterised by measuring cytokine
production, expression of granzyme B and cytotoxicity against tumour target cells. Results show that γδ T-cells are activated
by these mycobacterial preparations, as indicated by upregulation of activation marker expression and proliferation. Activated
γδ T-cells display enhanced effector responses, as shown by upregulated granzyme B expression, production of the TH1 cytokines IFN-γ and TNF-α, and enhanced degranulation in response to susceptible and zoledronic acid-treated resistant tumour
cells. Moreover, γδ T-cell activation is induced by IL-12, IL-1β and TNF-α from circulating type 1 myeloid dendritic cells
(DCs), but not from type 2 myeloid DCs or plasmacytoid DCs. Taken together, we show that BCG, M. vaccae and M. obuense induce γδ T-cell anti-tumour effector responses indirectly via a specific subset of circulating DCs and suggest a mechanism
for the potential immunotherapeutic effects of BCG, M. vaccae and M. obuense in cancer. 相似文献
11.
12.
Jie Qi Jinsong Zhang Weiguo Feng Xiangdong Luo Changlin Li Zongliang Zhang 《中国科学:生命科学英文版》2000,43(6):578-588
We detected the expression of IL-12 p40/p35 mRNA by semi-quantitative RT-PCR and silver staining, and studied the molecular
interaction between the IL-12 expression and the NF-eB activation induced by LPS and IFN-γ/LPS in murine peritoneal suppressor
macrophages (MPSMs). It was found that IFN-γ strongly enhanced the LPS-induced IL-12 p40 and p35 mRNA expression. Both p40
and p35 mRNA levels were approximately equal. IFN-a also greatly promoted the LPS-induced secretion of IL-12 p70 in MPSMs.
The Proteasome Inhibitor I (PSI) could block the expression of IL-12 p40 and p35 mRNA, and the degradation of IκBα induced
by LPS or LPS/IFN-γ. EMSA showed that LPS could augment the NF-κB binding activity to p40 promoter DNA. However, IFN-γ could
neither enhance the LPS-induced NF-κB activity nor promote the degradation of IκBα. Taken together, the data suggest: (i)
IFN-γ/LPS could strongly induce the expression of IL-12 p40 and p35 mRNA; both the expression levels were equal; this phenomenon
coincided with the high-level secretion of IL-12 p70 induced by IFN-γ/LPS; (ii) NF-κB signal pathway is essential for IFN-γ/LPS
to induce IL-12 mRNA expression; (iii) by blocking the degradation of IκB, the PSI suppresses the IL-12 p40/p35 mRNA expression
induced by LPS and IFN-γ/LPS; (iv) NF-κB signal may not be involved in the mechanism by which IFN-γ enhanced the expression
of the LPS-induced IL-12 p40/p35 mRNA.
The first two authors contributed equally to this work. 相似文献
13.
Hasem Habelhah Futoshi Okada Kazumoto Nakai Sung Ki Choi Jun-ichi Hamada Masanobu Kobayashi M. Hosokawa 《Cancer immunology, immunotherapy : CII》1998,46(6):338-344
Previously we reported the malignant progression of QR-32, a regressor-type tumor clone, following co-implantation with foreign
bodies (gelatin sponge or plastic plate) in normal syngeneic C57BL/6 mice. We also reported that the progression of QR-32
cells by a gelatin sponge was significantly inhibited in the mice administered polysaccharide K (PSK) and that PSK induced
an increase of radical scavengers, especially manganese superoxide dismutase (Mn-SOD), locally at the site of tumor tissues.
In this study, to reveal the possible mechanism by which PSK induced Mn-SOD in the tumor tissues, we examined the mRNA expression
and protein levels of inflammatory cytokines in the tissues. We found that mRNAs of tumor necrosis factor α (TNFα) and interleukin-1α
(IL-1α) were considerably expressed in both PSK-treated and phosphate-buffered-saline-treated tumors, and that the mRNA expression
and protein level of interferon γ (IFNγ) increased in the tumor tissues treated with PSK. In vitro treatment of QR-32 cells
with IFNγ did not significantly increase the production of Mn-SOD; however, the combination of IFNγ with TNFα increased the
Mn-SOD production more effectively than did any of the cytokines used singly. Furthermore, we observed the down-regulation
of the mRNA expression and protein level of transforming growth factor β (TGFβ) in the tumor tissues treated with PSK, and
that in vitro treatment of QR-32 cells with TGFβ decreased the production of Mn-SOD. These results suggest that PSK suppresses
the progression of QR-32 cells by increasing Mn-SOD via the modulation of inflammatory cytokines; that is, by decreasing TGF-β
and increasing IFN-γ.
Received: 7 October 1997 / Accepted: 31 March 1998 相似文献
14.
15.
16.
T-cell responses to antigens are classified on the basis of the cytokines they produce as either Th1 (IFN-γ, IL-2) or Th2 (IL-4, IL-10), with these Th types being indicative of either cell-mediated or antibody-mediated responses, respectively. Using this classification, T-cell responses in MHC-class-II-restricted autoimmune diseases appear to be predominantly of the Th1 type, based on the presence of high levels of IFN-γ. This simplistic classification has recently been challenged, however, as disease incidence and severity are frequently elevated in animals that have a deficient IFN-γ response. The recent data discussed here indicate that the cytokine circuits involved in the regulation of cell-mediated and humoral immune responses during the development of autoimmune arthritis are more complex than originally proposed; perhaps our characterization of autoimmune responses as strictly Th1 or Th2 is overly simplistic, especially as it pertains to the role of IFN-γ. 相似文献
17.
Immunotherapy, including the use of cytokines and/or modified tumour cells immune stimulatory cytokines, can enhance the host anti-tumour immune responses. Interleukin-23 (IL-23) is a relative novel cytokine, which consists of a heterodimer of the IL-12p40 subunit and a novel p19 subunit. IL-23 has biological activities similar to but distinct from IL-12. IL-23 can enhance the proliferation of memory T cells and the production of IFN-γ, IL-12 and TNF-α from activated T cells. IL-23 activates macrophages to produce TNF-α and nitric oxide. IL-23 can also act directly on dendritic cells and possesses potent anti-tumour and anti-metastatic activity in murine models of cancer. IL-23 can also induce a lower level of IFN-γ production compared with that induced by IL-12. This may make IL-23 an alternative and safer therapeutic agent for cancer, as IL-12 administration can lead to severe toxic side effects because of the extremely high levels of IFN-γ it induces.This article is a symposium paper from the Annual Meeting of the “International Society for Cell and Gene Therapy of Cancer”, held in Shenzhen, China, on 9–11 December 2005. 相似文献
18.
19.
Danielle Burger 《Arthritis research & therapy》2000,2(6):472-5
The intricate interactions that regulate relationships between endogenous tissue cells and infiltrating immune cells in the rheumatic joint, particularly in rheumatoid arthritis (RA), were the subject of the meeting. A better understanding of these interactions might help to define intervention points that could be used to develop specific therapies. The presentations and discussions highlighted the fact that, once chronic inflammation is established, several pro-inflammatory loops involving tumour necrosis factor (TNF)-α and interleukin (IL)-1β can be defined. Direct cellular contact with stimulated T lymphocytes induces TNF-α and IL-1β in monocytes which in turn induce functions in fibroblast-like synoviocytes. The latter include the production of stromal cell-derived factor-1α (SDF-1α) which enhances the expression of CD40L in T cells, which stimulates SDF-1α production in synoviocytes, which in turn protects T and B cells from apoptosis and enhances cell recruitment thus favoring inflammatory processes. IL-1β and TNF-α also induce IL-15 in fibroblast-like synoviocytes, which induces the production of IL-17 which in turn potentiates IL-1β and TNF-α production in monocyte-macrophages. This underlines the importance of TNF-α and IL-1β in RA pathogenesis, and helps explain the efficiency of agents blocking the activity of these cytokines in RA. Factors able to block the induction of cytokine production (such as apolipoprotein A-I [apo A-I] and interferon [IFN]-β) might interfere more distally in the inflammatory process. Furthermore, stimulated T lymphocytes produce osteoclast differentiation factor (ODF), which triggers erosive functions of osteoclasts. Therefore, factors capable of affecting the level of T lymphocyte activation, such as IFN-β, IL-15 antagonist, or SDF-1α antagonist, might be of interest in RA therapy. 相似文献
20.
Liu WQ Tian MX Wang YP Zhao Y Zou NL Zhao FF Cao SJ Wen XT Liu P Huang Y 《Molecular biology reports》2012,39(4):3611-3618
Newcastle disease virus (NDV) is an important pathogen hazardous to poultry industry, and the pathogenicity of NDV strains
varies with different virulence. Peripheral blood serves as an important producer and carrier of viruses and cytokines in
NDV infection. In order to explore the difference of cytokine expression in the peripheral blood between velogenic strain
and lentogenic strain infection, NDV virulent strain F48E9 and vaccine strain Lasota were used to infect specific-pathogen-free
(SPF) chickens separately, and peripheral blood was collected on 0, 3, 7, 10, 14, and 21 days post-infection (d.p.i.). Real-time
PCR was then used to detect the expression of six kinds of immune-related cytokine genes. For the F48E9 group, a sharp increase
of the expression of interferon-alpha (IFN-α), interferon-gamma (IFN-γ), interleukin-16 and IL-18 was observed on 3 d.p.i.
before the NDV blood peak (7 d.p.i.), followed by a rapid decline to the level lower than that of control group, then the
expression of IFN-α increased slowly and reached or exceeded the level of control group in the later phase of the infection,
while the expression of IFN-γ, IL-16, and IL-18 fluctuated at the level of control group for the rest of study period. The
increase of IL-2 expression was not obvious, and no increase of IL-15 expression was noted. For the Lasota (vaccine) group,
the picture was quite different, a sharp increase of IFN-γ (but not IFN-α), IL-2 was observed on 7 d.p.i. before the NDV blood
peak (10 d.p.i.). On the contrary, there was no dramatic increase of IL-16 and IL-18. Interestingly, in contrast to the F48E9
group, there was an increase of IL-15 on day 10 d.p.i., but it remained modest. There was also an increase of IFN-α on day
21 d.p.i. Our results revealed that infection with NDV strains of different virulence was associated with distinct cytokine
expression patterns in peripheral blood, modulation of cytokine responses may play a key role in mediation of NDV pathogenesis. 相似文献