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1.
Shinya Nagafuchi Mamoru Totsuka Satoshi Hachimura Masao Goto Takeshi Takahashi Takaji Yajima Tamotsu Kuwata Shuichi Kaminogawa 《Cytotechnology》2002,40(1-3):49-58
We have investigated the influence of dietary nucleotides on the intestinal immune system in ovalbumin (OVA)-specific T-cell
receptor (TCR) transgenic mice (OVA-TCR Tg mice). When mice were supplied with water supplemented with 2% OVA ad libitum, the faecal OVA-specific immunoglobulin A (IgA) level significantly increased in those fed a nucleotide-supplemented diet
(NT(+) diet) compared with those fed a nucleotide-free control diet (NT(–) diet). In the NT(+) diet-fed mice, secretion of
transforming growth factor β (TGF-β), which is an isotype-specific switch factor for IgA, from intestinal epithelial cells
(IECs) was significantly increased. Furthermore, an increased proportion of intestinal intraepithelial lymphocytes (IELs)
bearing γδ TCR (TCRγδ+ IELs) and increased secretion from IECs of interleukin 7 (IL-7), which is essential for the development of TCRγδ+ IELs, were also observed in OVA-TCR-Tg mice fed the NT(+) diet, as we previously demonstrated using BALB/c mice (Nagafuchi
et al., Biosci. Biotechnol. Biochem. 64: 1459-65 (2000)). Considering that TCRγδ+ T cells and TGF-β are important for an induction of the mucosal IgA response, our results suggest that dietary nucleotides
augment the mucosal OVA-specific IgA response by increasing the secretion of TGF-β from IECs and the proportion of TCRγδ+ IELs.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
2.
Matagrano LB Magida JA McGee DW 《In vitro cellular & developmental biology. Animal》2003,39(3-4):183-186
Summary Intestinal epithelial cells (IEC) are known to produce monocyte chemoattractant protein-1 (MCP-1). However, MCP-1 production,
as with many other cytokines, can be regulated by a network of cytokines present in the environment of the IEC. Both IEC and
inflammatory cells have been shown to produce transforming growth factor-β (TGF-β), and the regulatory effect of this cytokine
on MCP-1 secretion by IEC has not been determined. Using the IEC-18 cell line, we have found that TGF-β1 alone induced the
secretion of high levels of MCP-1. Treatment with TGF-β1 also enhanced the levels of MCP-1 messenger ribonucleic acid. However,
costimulation of the cells with TGF-β1 and interleukin-1β (IL-1β) resulted in significant, but less than additive, increases
in MCP-1 secretion. Finally, the enhancing effect of TGF-β1 on MCP-1 secretion was not due to IL-6. These results suggest
that TGF-β1 from IEC or inflammatory cells may significantly enhance the secretion of MCP-1 by IEC and play an important role
in inflamed mucosal tissues. 相似文献
3.
4.
Roman Paduch Martyna Kandefer-Szerszeń 《In vitro cellular & developmental biology. Animal》2009,45(9):543-550
Colon adenocarcinoma is one of the most common fatal malignancies in Western countries. Progression of this cancer is dependent
on tumor microenvironmental signaling molecules such as transforming growth factor-β (TGF-β) or acetylcholine (ACh). The present
study was conducted to assess the influence of recombinant human transforming growth factor (rhTGF)-β1 or ACh on nitric oxide
(NO) and interleukin-1β (IL-1β) secretion by three human colon adenocarcinoma cell lines: HT29, LS180, and SW948, derived
from different grade tumors (Duke’s stage). The cells were cultured in 2D and 3D (spheroids) conditions. Colon carcinoma cells
exhibited different sensitivities to rhTGF-β1 or ACh dependent on the tumor grade and the culture model. ACh exhibited significant
inhibitory effects towards NO, endothelial nitric oxide synthase (eNOS), and IL-1β secretion especially by tumor cells derived
form Duke’s C stage of colon carcinoma. rhTGF-β1 also decreased NO, IL-1β, and eNOS expression, but its effect was lower than
that observed after the administration of ACh. The inhibition of NO and IL-1β production was more striking in 3D tumor spheroids
than in 2D culture monolayers. Taken together, the TGF-β1–ACh axis may regulate colon carcinoma progression and metastasis
by altering NO secretion and influence inflammatory responses by modulating IL-1β production. 相似文献
5.
Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that plays a critical role in modulating immune response and
inflammation. We have investigated the effects of TGF-β1 on the expression of type IV collagenases, matrix metalloproteinase
(MMP)-2 and MMP-9, in mouse peritoneal macrophages. TGF-β1 alone enhanced the secretion of MMP-9, while it blocked lipopolysaccharide
(LPS)-stimulated MMP-9 production. We have shown that this biphasic effect of TGF-β1 is exerted at the mRNA level of the MMP-9
gene. Although TGF-β1 increased both basal and LPS-induced MMP-2 production at the protein and mRNA levels, the extent of
the increase was smaller in LPS-activated macrophages than in control macrophages. The expression of type I and type II receptors
for TGF-β was significantly decreased upon activation, suggesting that the lesser effect of TGF-β1 in activated macrophages
may result from the decreased expression of TGF-β receptors. In addition, the expression of endogenous TGF-β1 mRNA was decreased
significantly in activated macrophages. These findings suggest that activated macrophages not only produce less TGF-β1, but
also respond less well to TGF-β to provide for inflammatory response. 相似文献
6.
Balzer Sandrock Karen M. Hudson Douglas E. Williams Michael A. Lieberman 《In vitro cellular & developmental biology. Animal》1996,32(4):225-233
Summary The regulation of megakaryopoeisis by cytokines is not yet well understood. It is possible that autocrine loops are established
during megakaryocyte growth and differentiation, aiding in the maturation of these cells. The CHRF-288-11 human megakaryoblastic
cell line has been examined for cytokine production in growing cells and cells stimulated to differentiate by the addition
of phorbol esters. It has been demonstrated that these cells produce RNA corresponding to the interleukins IL-1α, 1β, 3, 7,
8, and 11, granulocyte-macrophage colony stimulating factor (GM-CSF), stem cell factor (SCF), transforming growth factor-β
(TGF-β), tumor necrosis factor-α (TNF-α), interferon-α (INF-α), and basic fibroblast growth factor (bFGF). Additionaly, RNA
corresponding to the receptors for IL-6, GM-CSF, SCF, INF-α,β, bFGF, and monocyte colony stimulating factor (M-CSF) were also
expressed by the cells. The receptor for TNF-α was detected immunologically. Analysis at the protein level demonstrated that
significant amounts of INF-α, TNF-α, GM-CSF, SCF, IL-1α, and a soluble form of the IL-6 receptor were produced by the cells.
Addition of phorbol esters to CHRF-288-11 cells enhances their megakaryocytic phenotype; such treatment also results in increased
secretion of INF-α, TNF-α, and GM-CSF. These results suggest that potential autocrine loops are established during the differentiation
of CHRF-288-11 cells, which may alter the capability of the cell to differentiate. These findings are similar to those recently
obtained for marrow-derived megakaryocytes (Jiang et al.) suggesting that CHRF-288-11 cells provide a useful model system
for the study of cytokine release during megakaryocyte differentiation. 相似文献
7.
8.
Th2 cytokines down-regulate TLR expression and function in human intestinal epithelial cells 总被引:4,自引:0,他引:4
Mueller T Terada T Rosenberg IM Shibolet O Podolsky DK 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(10):5805-5814
TLRs serve important immune and nonimmune functions in human intestinal epithelial cells (IECs). Proinflammatory Th1 cytokines have been shown to promote TLR expression and function in IECs, but the effect of key Th2 cytokines (IL-4, IL-5, IL-13) on TLR signaling in IECs has not been elucidated so far. We stimulated human model IECs with Th2 cytokines and examined TLR mRNA and protein expression by Northern blotting, RT-PCR, real-time RT-PCR, Western blotting, and flow cytometry. TLR function was determined by I-kappaBalpha phosphorylation assays, ELISA for IL-8 secretion after stimulation with TLR ligands and flow cytometry for LPS uptake. IL-4 and IL-13 significantly decreased TLR3 and TLR4 mRNA and protein expression including the requisite TLR4 coreceptor MD-2. TLR4/MD-2-mediated LPS uptake and TLR ligand-induced I-kappaBalpha phosphorylation and IL-8 secretion were significantly diminished in Th2 cytokine-primed IECs. The down-regulatory effect of Th2 cytokines on TLR expression and function in IECs also counteracted enhanced TLR signaling induced by stimulation with the hallmark Th1 cytokine IFN-gamma. In summary, Th2 cytokines appear to dampen TLR expression and function in resting and Th1 cytokine-primed human IECs. Diminished TLR function in IECs under the influence of Th2 cytokines may protect the host from excessive TLR signaling, but likely also impairs the host intestinal innate immune defense and increases IEC susceptibility to chronic inflammation in response to the intestinal microenvironment. Taken together, our data underscore the important role of Th2 cytokines in balancing TLR signaling in human IECs. 相似文献
9.
Enteropathogenic Escherichia coli (EPEC) triggers a large release of adenosine triphosphate (ATP) from host intestinal cells and the extracellular ATP is broken
down to adenosine diphosphate (ADP), AMP, and adenosine. Adenosine is a potent secretagogue in the small and large intestine.
We suspected that ecto-5′-nucleotidase (CD73, an intestinal enzyme) was a critical enzyme involved in the conversion of AMP
to adenosine and in the pathogenesis of EPEC diarrhea. We developed a nonradioactive method for measuring ecto-5′-nucleotidase
in cultured T84 cell monolayers based on the detection of phosphate release from 5′-AMP. EPEC infection triggered a release
of ecto-5′-nucleotidase from the cell surface into the supernatant medium. EPEC-induced 5′-nucleotidase release was not correlated
with host cell death but instead with activation of phosphatidylinositol-specific phospholipase C (PI-PLC). Ecto-5′-nucleotidase
was susceptible to inhibition by zinc acetate and by α,β-methylene-adenosine diphosphate (α,β-methylene-ADP). In the Ussing
chamber, these inhibitors could reverse the chloride secretory responses triggered by 5′-AMP. In addition, α,β-methylene-ADP
and zinc blocked the ability of 5′-AMP to stimulate EPEC growth under nutrient-limited conditions in vitro. Ecto-5′-nucleotidase
appears to be the major enzyme responsible for generation of adenosine from adenine nucleotides in the T84 cell line, and
inhibitors of ecto-5′-nucleotidase, such as α,β-methylene-ADP and zinc, might be useful for treatment of the watery diarrhea
produced by EPEC infection. 相似文献
10.
11.
A. V. Zhigailov E. S. Babaylova N. S. Polimbetova D. M. Graifer G. G. Karpova B. K. Iskakov 《Molecular Biology》2011,45(2):291-299
A putative implication 3′-terminal 18S rRNA segment in the cap-independent initiation of translation on plant ribosomes was
studied. It was shown that 3′-terminal segment (nucleotides 1777–1811) of 18S rRNA including the last hairpin 45 was accessible
for complementary interactions within 40S ribosomal subunits. Oligonucleotides complementary to this segment of rRNA, when
added to wheat germ cell-free protein synthesizing system, specifically inhibited translation of uncapped reporter mRNA encoding
β-glucuronidase. In the 5′-untranslated region (UTR), the reporter mRNA contained a leader sequence of potato virus Y (PVY)
genomic RNA with fragments complementary to the region 1777–1811. A sequence corresponding to nucleotides 291–316 of PVY,
which was complementary to most of the 3′-terminal 18S rRNA segment 1777–1808, was shown to enhance translational efficiency
of the reporter mRNAs when placed into 5′-UTR. The obtained results suggest that complementary interactions between 5′-UTR
of mRNA and 3′-terminal segment of 18S rRNA can take place during cap-independent translation initiation. 相似文献
12.
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
13.
Ceccarelli F Perricone C Fabris M Alessandri C Iagnocco A Fabro C Pontarini E De Vita S Valesini G 《Arthritis research & therapy》2011,13(4):R111
Introduction
Single nucleotide polymorphisms (SNPs) of transforming growth factor β (TGF-β) and IL-6 genes (respectively, 869C/T and -174G/C) have been associated with radiographic severity of bone-erosive damage in patients with rheumatoid arthritis (RA). Musculoskeletal ultrasound (US) is more sensitive than radiography in detecting bone erosion. We analyzed the association between TGF-β 869C/T and IL-6 -174G/C SNPs and bone-erosive damage, evaluated by US, in a cohort of patients with severely active RA. 相似文献14.
Transforming growth factor-β (TGF-β) is a central regulator in chronic liver disease contributing to all stages of disease
progression from initial liver injury through inflammation and fibrosis to cirrhosis and hepatocellular carcinoma. Liver-damage-induced
levels of active TGF-β enhance hepatocyte destruction and mediate hepatic stellate cell and fibroblast activation resulting
in a wound-healing response, including myofibroblast generation and extracellular matrix deposition. Being recognised as a
major profibrogenic cytokine, the targeting of the TGF-β signalling pathway has been explored with respect to the inhibition
of liver disease progression. Whereas interference with TGF-β signalling in various short-term animal models has provided
promising results, liver disease progression in humans is a process of decades with different phases in which TGF-β or its
targeting might have both beneficial and adverse outcomes. Based on recent literature, we summarise the cell-type-directed
double-edged role of TGF-β in various liver disease stages. We emphasise that, in order to achieve therapeutic effects, we
need to target TGF-β signalling in the right cell type at the right time. 相似文献
15.
Lysozyme transgenic goats’ milk positively impacts intestinal cytokine expression and morphology 总被引:1,自引:0,他引:1
In addition to its well-recognized antimicrobial properties, lysozyme can also modulate the inflammatory response. This ability
may be particularly important in the gastrointestinal tract where inappropriate inflammatory reactions can damage the intestinal
epithelium, leading to significant health problems. The consumption of milk from transgenic goats producing human lysozyme
(hLZ) in their milk therefore has the potential to positively impact intestinal health. In order to investigate the effect
of hLZ-containing milk on the inflammatory response, young pigs were fed pasteurized milk from hLZ or non-transgenic control
goats and quantitative real-time PCR was performed to assess local expression of TNF-α, IL-8, and TGF-β1 in the small intestine.
Histological changes were also investigated, specifically looking at villi width, length, crypt depth, and lamina propria
thickness along with cell counts for intraepithelial lymphocytes and goblet cells. Significantly higher expression of anti-inflammatory
cytokine TGF-β1 was seen in the ileum of pigs fed pasteurized milk containing hLZ (P = 0.0478), along with an increase in intraepithelial lymphocytes (P = 0.0255), and decrease in lamina propria thickness in the duodenum (P = 0.0001). Based on these results we conclude that consuming pasteurized milk containing hLZ does not induce an inflammatory
response and improves the health of the small intestine in pigs. 相似文献
16.
Keratinocytes migrating from a wound edge or initiating malignant invasion greatly increase their expression of the basement
membrane protein Laminin-322 (Lam332). In culture, keratinocytes initiate sustained directional hypermotility when plated
onto an incompletely processed form of Lam332 (Lam332′) or when treated with transforming growth factor beta (TGF-β), an inducer
of Lam332 expression. The development and tissue architecture of stratified squamous and prostate epithelia are very different,
yet the basal cells of both express p63, α6β4 integrin, and Lam332. Keratinocytes and prostate epithelial cells grow well
in nutritionally optimized culture media with pituitary extract and certain mitogens. We report that prostate epithelial cells
display hypermotility responses indistinguishable from those of keratinocytes. Several culture medium variables attenuated
TGF-β-induced hypermotility, including Ca++, serum, and some pituitary extract preparations, without impairing growth, TGF-β growth inhibition, or hypermotility on Lam322′.
Distinct from its role as a mitogen, EGF proved to be a required cofactor for TGF-β-induced hypermotility and could not be
replaced by HGF or KGF. Prostate epithelial cells have a short replicative lifespan, restricted both by p16INK4A and telomere-related mechanisms. We immortalized the normal prostate epithelial cell line HPrE-1 by transduction to express
bmi1 and TERT. Prostate epithelial cells lose expression of p63, β4 integrin, and Lam332 when they transform to invasive carcinoma.
In contrast, HPrE-1/bmi1/TERT cells retained expression of these proteins and normal TGF-β signaling and hypermotility for
>100 doublings. Thus, keratinocytes and prostate epithelial cells possess common hypermotility and senescence mechanisms and
immortalized prostate cell lines can be engineered using defined methods to yield cells retaining normal properties. 相似文献
17.
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
18.
19.
Dandawate S Williams L Joshee N Rimando AM Mittal S Thakur A Lum LG Parajuli P 《Cancer immunology, immunotherapy : CII》2012,61(5):701-711
A number of studies have implicated tumor-induced Treg cell activity in the sub-optimal response to therapeutic vaccines. Development of neo-adjuvant strategies targeting Treg cells is therefore imperative. Scutellaria extracts or constituent flavonoids have shown encouraging efficacy against various
tumors, including gliomas, in both pre-clinical and clinical studies. We report here, for the first time, that Scutellaria ocmulgee leaf extract (SocL) and flavonoid wogonin could inhibit TGF-β1-induced Treg activity in malignant gliomas. F344 rats, subcutaneously transplanted with F98 gliomas, were treated with SocL. There was
a significant inhibition of intra-tumoral TGF-β1 and Treg cell frequency as well as peripheral blood TGF-β1 levels in SocL-treated animals compared to the controls. SocL extract and
wogonin also inhibited glioma-induced, TGF-β1-mediated Treg activity in vitro. SocL extract and wogonin also inhibited the secretion of IL-10 in Treg culture; whereas the level of IL-2 was either unchanged or marginally enhanced. We also observed an inhibition of Smad-3,
GSK-3β and ERK1/2 signaling by SocL and wogonin in Treg cells, while phosphorylation of P38 MAPK was considerably enhanced, indicating that SocL or wogonin could inhibit the T cells’
response to TGF-β1 via modulation of both Smad and non-Smad signaling pathways. Overall, this study suggests that Scutellaria
can potentially reverse tumor-mediated immune suppression via inhibition of TGF-β1 secretion as well as via inhibition of
T cells’ response to TGF-β1. This may provide an opportunity for developing a novel adjuvant therapeutic strategy for malignant
gliomas, combining Scutellaria with immunotherapy and chemo/radio-therapeutic regimen, which could potentially improve the
disease outcome. 相似文献