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1.
Akira Andoh Yoshihide Fujiyama Kazunori Hata Ken-ichi Sumiyoshi Tadao Bamba 《Journal of gastroenterology》1996,31(5):633-638
Intestinal epithelial cells are an important source of many biologically active molecules that modulate immune responses in
the mucosa. The purpose of this study was to demonstrate the synthesis of complement C3 component in the rat non-transformed
crypt-like intestinal epithelial cell line, IEC-6. Unstimulated IEC-6 cells secreted a low level of C3 protein and showed
weak expression of C3 mRNA. The addition of interleukin (IL)-1β induced a dose- and time-dependent increase in C3 production.
These effects of IL-1β were observed at a concentration as low as 0.01 ng/ml and reached a plateau at a concentration of 5
ng/ml. The effects were observed at the mRNA level as early as 6 h after the beginning of incubation. Transforming growth
factor (TGF)-β alone had no effect. However, TGF-β at low concentrations (0.001–1 ng/ml) enhanced the effect of IL-1β in increasing
C3 production; this enhancement was not observed at high concentrations (5–10 ng/ml). These effects of TGF-β were also observed
at the mRNA level. The present findings indicate that intestinal epithelial cells are indeed capable of synthesizing complement
C3 in response to IL-1β and TGF-β. 相似文献
2.
Regulation of expression of cytokines and growth factors in osteoarthritic cartilage explants 总被引:2,自引:0,他引:2
Osteoarthritis (OA) is a degenerative joint disease characterised by the breakdown of the extracellular matrix of chondrocytes
in the affected joints. Cytokines and growth factors which are known to play a role in the synthesis and degradation of cartilage
matrix have been shown to be upregulated in osteoarthritic cartilage. This upregulation resulted in two different phenotypes,
overexpressing either TNF-α and IL-6 or IL-1β, TGFβ1, IL-4 and IL-10. To investigate the hierarchy among growth factors and cytokines involved in cartilage metabolism, we analysed
osteoarthritic cartilage explants for their responses to human recombinant (rh) cytokines and growth factors. The cytokine
expression patterns of the explants before and after in vitro culture were compared by immunohistological staining of cartilage
sections. We found a coordinate expression of TNF-α and IL-6 on the one hand, and of IL-1β, TGFβ1, IL-4 and IL-10 on the other. Although TNF-α and IL-6 stimulated each other’s expression, they downregulated TGF β1, IL-4 and IL-10 or IL-1β, TGF β1 and IFNg, respectively. IL-1β upregulated the expression of TGF β1, IL-4 and IL-10, and jointly these four cytokines and growth factors downregulated IL-6. Both of the expression patterns
described for OA cartilage can be explained by these regulatory mechanisms. Interestingly, no cytokine efficiently downregulated
TNF-α, and even though IL-1β is upregulated in one of the OA phenotypes, none of the growth factors and cytokines tested –
except for IL-1β itself – seemed capable of mediating this upregulation. This unresponsiveness to cytokine stimulation might
hint at a genetic cause for the elevated expression in the respective phenotypes.
Received: 15 September 2000 / Accepted: 17 April 2001 相似文献
3.
Serum levels of tumor necrosis factor alpha,interleukin-1 alpha and beta in healthy elderly subjects
To determine the age-related changes in monokine secretion, the serum concentrations of tumor necrosis factor alpha (TNF),
interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) were measured in 31 young healthy subjects (21–35 years old) and
19 healthy elderly subjects (65–83 years old). There were no differences between the two groups with respect to serum concentrations
of these cytokines. We also measured in a subgroup of young (n=8–11) and elderly (n=8–10) subjects the in vitro secretion of TNF and IL-1β in response to adding to the medium lipopolysaccharide (LPS, 2 ng/ml), interferon gamma (50 U/ml)
or advanced glycosylation endproduct of bovine serum albumin (250 ug/ml). Only LPS-stimulated IL-1β production was significantly
reduced in elderly subjects (456.7 ± 229.9 vs 1118.8 ± 494.8 pg/ml). It is concluded that with the possible exception of LPS-stimulated
IL-1β production, monokine secretion measured in this study is well preserved in elderly subjects. 相似文献
4.
A. M. Rabuazzo M. Buscema V. Caltabiano M. Anello C. Degano G. Patanè R. Vigneri F. Purrello 《Diabetologia》1995,38(7):779-784
Summary In vitro exposure of rat pancreatic beta cells to interleukin-1β (IL-1β) inhibits glucose-stimulated insulin release (2140
± 239 and 323 ± 80 pg · islet–1· h–1 at glucose levels of 16.7 mmol/l in control and IL-1β-exposed islets, respectively, n = 7, p < 0.001). Cholera toxin (2 μg/ml) or pertussis toxin (0.5 μg/ml) potentiated, as expected, glucose-induced insulin release
in control islets, but, in addition, when added together with IL-1β, were able to prevent the IL-1β mediated inhibition of
glucose-stimulated insulin secretion (2087 ± 301 and 1662 ± 173 pg · islet–1· h–1, respectively, p < 0.05 vs islets exposed to IL-1β alone). To investigate the mechanism by which the toxins prevent the IL-1β effect, we then
measured nitrite levels, glucose oxidation and Ca2 + uptake. Nitrite levels in the culture medium were 4.2± 1.4 and 24.0 ± 5 pmol · islet–1· 24 h–1 in control islets and in IL-1β-exposed islets, respectively (n = 6, p = 0.05). In islets exposed to IL-1β and cholera or pertussis toxins, nitrite levels were 9.1 ± 3 and 12.4 ± 6 pmol · islet–1· 24 h–1, respectively (n = 6, NS vs control islets). Glucose oxidation at 16.7 mmol/l glucose was 31.1 ± 2.9 pmol · islet–1· 120 min–1 in control islets and 16.8 ± 2.7 pmol · islet–1· 120 min–1 in IL-1β-treated islets (p < 0.05). The addition of cholera or pertussis toxins simultaneously to IL-1β prevented the inhibition of glucose oxidation
at 16.7 mmol/l glucose (32.9 ± 3.8 and 31.7 ± 3.3 pmol · islet–1· 120 min–1 in the presence of cholera or pertussis toxins, respectively). Glucose-stimulated 45Ca2 + up-take was also significantly inhibited in IL-1β-treat-ed islets when compared to control islets (7.1 ± 0.9 and 16.8 ± 3.2 pmol · islet–1· 20 min–1, respectively, p < 0.05). This inhibition was prevented by the presence of cholera or pertussis toxins (14.0 ± 3.8 and 11.2 ± 2.7 pmol · islet–1· 20 min–1, respectively). In conclusion, our data show that cholera and, to a lesser extent, pertussis toxins are able to partially
prevent the IL-1β-induced increase in nitrite levels and block the inhibitory effects of IL-1β on different steps leading
to glucose-induced insulin secretion. These findings support the possibility that in pancreatic beta cells, G-proteins may
be involved or interfere with the cytokine signal transduction. [Diabetologia (1995) 38: 779–784]
Received: 20 October 1994 and in revised form: 5 January 1995 相似文献
5.
Human endometrium and endometrial epithelial cells (EECs) either cultured alone or cocultured with human embryos express leptin
and leptin receptor. This study compares the effect of leptin with that of interleukin-1β (IL-1β) on the expression of β3-EEC
integrin, a marker of endometrial receptivity. Both cytokines increased the expression of β3-EEC at concentrations in the
range of 0.06–3 nM; however, leptin exhibited a significantly greater effect than IL-1β. We also determined the regulatory effects of IL-1β
on leptin secretion and on the expression of leptin and leptin receptor at the protein level in both EEC and endometrial stromal
cell (ESC) cultures. In EEC cultures, IL-1β upregulated secretion of leptin and expression of both leptin and leptin receptors.
No effect of IL-1β was found in the ESC cultures. However, leptin exhibited marginal upregulation of leptin receptor. The
upregulation of β3-integrin and leptin/leptin receptor expression by IL-1β in EEC cultures indicates that both cytokines may
be implicated in embryonic-maternal cross-talk during the early phase of human implantation. Our present data also raise the
possibility that leptin is an endometrial molecular effector of IL-1β action on β3-integrin upregulation. Thus, a new role
for leptin in human reproduction as an autocrine/paracrine regulator of endometrial receptivity is proposed. 相似文献
6.
M. Neidhart 《Annals of hematology》1997,75(4):155-159
The expected association between age and the CD45 isoforms expression on CD4+ T-PBL is much more obvious in men than in women.
We investigated whether or not circulating factors influence the differentiation of CD4+ T-PBL. Peripheral blood samples were
obtained from 56 healthy age-matched subjects (28 men and 28 women, 21–55 years old). Mononuclear leukocytes were analyzed
by three-color flow cytometry. The serum concentrations of interleukin-1β (IL-1β), interleukin-6, tumor necrosis factor-α
(TNF-α), GM colony-stimulating factor, prolactin (Prl), and luteinizing hormone (LH) were determined by ELISA. The expected
age-related decrease of naive (CD45RA+,RO–) cells and increase of memory (CD45RA–,RO+) cells among CD4+ T-PBL were observed
in men only (p<0.001 and 0.005). In women, these correlations were not significant. On the other hand, in women only, elevated IL-1β was
associated with fewer naive and more memory cells among CD4+ T-PBL (p<0.001). In both sexes, IL-1β correlated with the expression of CD25 on CD4+ T-PBL (on either naive or memory cells, p<0.001). Other cytokines or the CD8+ T-PBL showed no significant correlation. In women, the elevation of LH at mid-cycle inversely
correlated with the proportion of naive CD4+ T-PBL (p<0.01). Elevated LH was associated with more CD25 on memory CD4+ T-PBL (p<0.01). A significant correlation exists between IL-1β and LH (p<0.001). Furthermore, in both sexes, Prl correlated with the proportion of CD4+ cells among T-PBL. In men, elevated Prl was
associated with more naive CD4+ T-PBL (p<0.005), while in women, Prl correlated with more transient CD45RA+, RO+ cells among CD4+ T-PBL and increased TNF-α (p<0.05 for both). Thus, circulating IL-1β could be involved in the expression of CD25 on CD4+ T-PBL and favors the generation
of memory CD4+ T-PBL. In women, the IL-1β- and/or mid-cycle-dependent processes seem to overwhelm the age-related changes.
Elevated Prl might exert a dual influence: it favors the development of naive CD4+ T lymphocytes and possibly acts in, synergy
with other cytokines during immune stimulation.
Received: 20 June 1997 / Accepted: 1 August 1997 相似文献
7.
Annexin 1 is an important mediator of glucocorticoid action in the hypothalamo-pituitary axis; however, little is known of
its role in mediating glucocorticoid actions in the peripheral endocrine organs. Accordingly, we have carried out a preliminary
study to investigate the effects of annexin 1 in vitro on the testicular secretion of testosterone, a process inhibitied by
both glucocorticoids and interleukin-1β (IL-1β). Luteinizing hormone (LH) and forskolin stimulated the release of testosterone
from dispersed murine testicular cells in vitro. Their effects were reduced in cells from mice pretreated with dexamethasone
(DEX). Similarly, preincubation of testicular cells from untreated mice with DEX, corticosterone, or 11-dehydrocorticosterone
reduced LH-stimulated testosterone release, as did the 11β-hydroxysteroid dehydrogenase inhibitors, glycyrrhetinic acid and
carbenoxolone. The inhibitory actions of the steroids were mimicked by annexin 11–188 (ANXA11–188) (a stable annexin 1 analog). IL-1β produced a marked decrease in the response to LH, which was blocked by indomethacin,
a nonselective cyclooxygenase inhibitor and an additive effect with DEX and ANXA11–188. These results confirm reports that glucocorticoids and IL-1β inhibit LH-stimulated testosterone release from mouse testicular
cells. They also show, for the first time, that the effects of the steroids are mimicked by annexin 1 and that, in contrast
to their mutually antagonistic effects in the neuroendocrine system, IL-1β and annexin 1 exert additive actions in the testis. 相似文献
8.
Hyun Mi Choi Da Hee Oh Jun Soo Bang Hyung-In Yang Myung Chul Yoo Kyoung Soo Kim 《Rheumatology international》2010,30(8):1025-1033
Inflammation in the joint of rheumatoid arthritis is a complex immune reaction facilitated by various factors, such as cytokines,
cells and hypoxia. Thus, we evaluated their relative capacity to produce proinflammatory mediators in response to IL-1β, TNF-α
or IL-17 under hypoxia or normoxia in fibroblast-like synoviocytes (FLSs) and macrophages. The level of IL-6 expression was
strongly increased in both FLSs and THP-1 macrophages in response to IL-1β and TNF-α, but the level by TNF-α was less than
that by IL-1β. In contrast, the expression of IL-8 in both cell types was strongly stimulated by both IL-1β and TNF-α. In
FLSs, PGE2 production increased only in response to IL-1β; and no effect was observed in THP-1 cells and TNF-α-stimulated FLSs. In addition,
the production by IL-17 was extremely low when compared with those induced by IL-1β or TNF-α in FLSs and THP-1 cells. Hypoxia
(2% O2) decreased IL-1β-stimulated production of PGE2, even though it increased the expression of mRNA and protein of COX-2. These results suggest that IL-1β and TNF-α differentially
regulate gene expression in FLSs and macrophages under hypoxia or normoxia. 相似文献
9.
Petersen LG Størling J Heding P Li S Berezin V Saldeen J Billestrup N Bock E Mandrup-Poulsen T 《Diabetologia》2006,49(8):1864-1875
Aims/hypothesis IL-1β released from immune cells induces beta cell pro-apoptotic signalling via mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB). In neurons, the neural cell adhesion molecule (NCAM) signals to several elements involved in IL-1β-induced pro-apoptotic signalling in beta cells. Pancreatic beta cells express NCAM, but its biological effects in these cells are unclear. The aim of this study was to investigate whether there is cross-talk between NCAM signalling and cytokine-induced pro-apoptotic signalling.Materials and methods Western blotting was used to investigate levels of NCAM and inducible nitric oxide synthase, phosphorylation of Src and MAPKs, and cleavage of caspase-3. MAPK activity was investigated with an in vitro kinase assay. Apoptosis was detected by cleaved caspase-3 and a Cell Death Detection ELISAplus assay. NCAM-induced fibroblast growth factor receptor (FGFR) activation was investigated in NCAM−/− Trex293 cells where FGFR phosphorylation was measured by Western blotting after NCAM transfection.Results Pre-exposure of INS-1E cells to the FGFR-inhibitor SU5402, but not to the Src-inhibitor PP2, dose-dependently inhibited IL-1β-mediated MAPK activity. A synthetic peptide, C3d, reported to bind NCAM, did not activate MAPK or Akt as reported in neurons but inhibited IL-1β-induced MAPK activity, thereby mimicking the effect of SU5402. Furthermore, C3d inhibited NCAM-induced FGFR phosphorylation and apoptosis induced by IL-1β plus IFN-γ, but did not affect IL-1β-induced NF-κB signalling.Conclusions/interpretation We suggest that NCAM signalling through FGFR is required for efficient IL-1β pro-apoptotic signalling by facilitating IL-1β-induced MAPK activation downstream of the NF-κB-MAPK branching point. Further, these data identify a novel function of C3d as an inhibitor of NCAM-induced FGFR activity and of IL-1β-induced MAPK activation in beta cells. 相似文献
10.
Regulation of insulin signalling, glucose uptake and metabolism in rat skeletal muscle cells upon prolonged exposure to resistin 总被引:8,自引:0,他引:8
Aims/hypothesis Debate exists regarding the role of resistin in the pathophysiology of insulin resistance. The aim of this study was to directly
assess the effects of resistin (0–24 h) on basal and insulin-stimulated glucose uptake and metabolism in skeletal muscle cells
and to investigate the mechanisms responsible for the effects of resistin.
Methods We used L6 rat skeletal muscle cells and examined [3H]2-deoxyglucose uptake, GLUT4 translocation and GLUT protein content. We assessed glucose metabolism by measuring the incorporation
of D-[U-14C]glucose into glycogen, 14CO2 and lactate production, as well as the phosphorylation level and total protein content of insulin signalling proteins, including
insulin receptor β-subunit (IRβ), insulin receptor substrate (IRS), Akt and glycogen synthase kinase-3β (GSK-3β).
Results Treatment of L6 rat skeletal muscle cells with recombinant resistin (50 nmol/l, 0–24 h) reduced levels of basal and insulin-stimulated
2-deoxyglucose uptake and decreased insulin-stimulated GLUT4myc content at the cell surface, with no alteration in the production
of GLUT4 or GLUT1. Resistin also decreased glycogen synthesis and GSK-3β phosphorylation. Insulin-stimulated oxidation of
glucose via the Krebs cycle was reduced by resistin, whereas lactate production was unaltered. Although insulin receptor protein
level and phosphorylation were unaltered by resistin, production of IRS-1, but not IRS-2, was downregulated and a decreased
tyrosine phosphorylation of IRS-1 was detected. Reduced phosphorylation of Akt on T308 and S473 was observed, while total
Akt and Akt1, but not Akt2 or Akt3, production was decreased.
Conclusions/interpretation Our data show that resistin regulates the function of IRS-1 and Akt1 and decreases GLUT4 translocation and glucose uptake
in response to insulin. Selective decreases in insulin-stimulated glucose metabolism via oxidation and conversion to glycogen
were also induced by resistin. These observations highlight the potential role of resistin in the pathophysiology of type
2 diabetes in obesity. 相似文献
11.
Kim OY Chae JS Paik JK Seo HS Jang Y Cavaillon JM Lee JH 《Age (Dordrecht, Netherlands)》2012,34(2):415-425
Inappropriate interleukin-6 production is thought to play a role in the development of several age-related conditions including
atherosclerosis. This study aimed to determine whether aging affects circulating interleukin-6 (IL-6) levels. Healthy, nonobese
women (n = 208, 44.5 ± 0.70 years, 22.4 ± 0.17 kg/m2) were categorized into four age groups (22–31, 32–41, 42–51, and 52–63 years; cross-sectional study). Cytokine levels in
serum and those produced from peripheral blood mononuclear cell (PBMC) were measured. The oldest group had the highest circulating
levels of IL-6 and oxidized low-density lipoprotein (ox-LDL) and higher PBMC production of IL-6, tumor necrosis factor-α (TNF-α),
and interleukin-1 alpha (IL-1β). Additionally, significant interactions between age and menopause were found for serum IL-6
(P = 0.024), and TNF-α (P = 0.011) and IL-1β (P < 0.001) produced from PBMCs. Serum IL-6 levels positively correlated with age, waist–hip ratio (WHR), systolic blood pressure,
circulating levels of TNF-α, IL-1β, and ox-LDL, and urinary 8-epi-prostaglandin F2α. Multiple stepwise regression models identified the following factors for contributing to serum IL-6 levels: serum IL-1β,
menopause status, WHR, and serum TNF-α in mode I (R
2 = 0.302); serum IL-1β, age, serum TNF-α, and WHR (β = 0.197; P = 0.006) in model II (R
2 = 0.283). Sub-analysis was performed according to menopausal status. Serum IL-6 levels were positively associated with levels
of IL-6, TNF-α, and IL-1β in PBMC supernatants (unstimulated) from postmenopausal women, whereas these were negatively associated
in premenopausal women. In conclusion, circulating IL-6 levels may be interactively influenced by age and menopause. Additionally,
estrogen deprivation after menopause may enhance PBMC cytokine production in postmenopausal women, resulting in increased
IL-6 levels which are closely related to oxidative stress. 相似文献
12.
13.
Association between interleukin-1β-511C/T polymorphism and reflux esophagitis in Japan 总被引:1,自引:0,他引:1
Muramatsu A Azuma T Okuda T Satomi S Ohtani M Lee S Suto H Ito Y Yamazaki Y Kuriyama M 《Journal of gastroenterology》2005,40(9):873-877
Background Interleukin-1β (IL-1β) gene polymorphisms are related to hypochlorhydria and increase the risk of gastric cancer in the presence
of Helicobacter pylori infection. However, little information is available about the genetic risk factors of reflux esophagitis. In this study we
investigated its association with the IL-1β polymorphisms.
Methods We examined 48 patients with reflux esophagitis and 96 control subjects, 89 with gastric cancer. IL-1β-511C/T genotyping was
performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
Results The frequency of IL-1β-511T alleles was significantly higher in reflux esophagitis patients (57.3%) than in controls (41.1%)
(P = 0.0215, χ2 = 5.289). The frequency of IL-1β-511T/T genotypes was also significantly higher in reflux esophagitis patients (31.3%) than
in controls (15.6%). The odds ratio and the 95% confidence interval were 4.000 and 1.393–11.486, respectively. The frequency
of IL-1β-511T/T genotypes was significantly higher in reflux esophagitis patients (31.3%) than in gastric cancer patients
(21.4%). The odds ratio and the 95% confidence interval were 2.961 and 1.054–8.316, respectively.
Conclusions IL-1β-511T was associated with reflux esophagitis having hyperacidity. Differences of genetic background regarding gastric
acid secretion may exist between Japanese and Caucasians. 相似文献
14.
Immune-endocrine interactions are important to the regulation of Leydig cell steroidogenesis. We have shown previously that
both tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1-β) inhibit 8-bromo-cAMP-(8-Br-cAMP)-stimulated steroidogenesis
in mouse Leydig cells. TNF and IL-1 both inhibit cAMP-stimulated testosterone production as well as mRNA and protein levels
of cholesterol side chain cleavage enzyme (P450scc) and 17α-hydroxylase/C17,20 lyase (P450c17) in mouse Leydig cells. Neither TNF nor IL-1 affects basal levels of P450scc mRNA and protein. In the present
study, we tested the effects of TNF and IL-1 on basal testosterone production and 8-Br-cAMP-stimulated 3β-hydroxysteroid dehydrogenase/Δ5→Δ4 isomerase(3βHSD) expression in Leydig cells. Purified and macrophage-depleted Leydig cells were cultured for 5 d with daily
changes of media, and then treated with increasing concentrations of recombinant mouse TNF or IL-1 in the presence or absence
of 8-Br-cAMP (50 μM) for 24 h. The media were collected for testosterone RIA and RNA and protein were extracted from cells. Basal testosterone
production was inhibited by TNF, but not IL-1. Treatment of Leydig cells with 8-Br-cAMP alone caused a marked increase in
3βHSD mRNA, and protein levels. Both TNF and IL-1 inhibited cAMP-stimulated 3βHSD mRNA and protein levels, but only TNF inhibited
basal 3βHSD expression. These results demonstrate that TNF and IL-1 have different effects on basal steroidogenesis in Leydig
cells and suggest that TNF-mediated inhibition of basal testosterone production may be owing to the inhibition of basal 3β-HSD
expression in Leydig cells. 相似文献
15.
van Grevenstein WM Hofland LJ van Rossen ME van Koetsveld PM Jeekel J van Eijck CH 《Digestive diseases and sciences》2007,52(10):2775-2783
Surgical handling of the peritoneum causes an inflammatory reaction, during which a potentially lethal cocktail of active
mediators is produced, including cytokines and growth factors. The aim of this study was to investigate the effects of inflammatory
cytokines on the interaction between tumor and mesothelial cells. Tumor cell adhesion to a mesothelial monolayer was assessed
after preincubation of the mesothelium with interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α.
Preincubation of the mesothelial monolayer with IL-1β or TNF-α resulted in enhanced tumor cell adhesion of Caco2 and HT29
colon carcinoma cells. The amount of stimulation for the Caco2 cells was between 20% and 40% and for HT29 cells between 30%
and 70%. Blocking experiments with anti–IL-1β and anti–TNF-α resulted in significant inhibition of the cytokine-stimulated
tumor cell adhesion. The presented results prove that IL-1β and TNF-α are significant stimulating factors in tumor cell adhesion
in vitro and may therefore account for tumor recurrence to the peritoneum in vivo. 相似文献
16.
Apoptosis of arterial cells induced by oxidized low–density
lipoprotein (oxLDL) is thought to contribute to the progression of vascular
dysfunction and atherogenesis. It is well established that diabetes mellitus is
accompanied by both glycosylation and oxidation LDL, but the biological
effects of these modified lipoproteins are poorly understood. We demonstrate
here that glycosylated oxLDL (glc–oxLDL) promotes apoptotic signaling in
human coronary smooth muscle cells. This was associated by a decrease of
the antiapoptotic protein Bcl–2, an increase of the pro–apoptotic protein Bax,
and activation of caspase 3. Glc–oxLDL also activated NFkB and decreased
IkB, these effects were more pronounced than those achieved with oxLDL.
Our study shows that glc–oxLDL influences a broad cascade of signaling
transduction pathways, which may not only result in apoptosis, but also could
affect NFkB in human coronary cells. This cascade of events may influence
the evolution of atherogenesis and vascular complications in diabetic
patients. 相似文献
17.
Young D. Jung Wenbiao Liu Niels Reinmuth Syed A. Ahmad Fan Fan Gary E. Gallick Lee M. Ellis 《Angiogenesis》2001,4(2):155-162
Small tumor vessels are composed of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). These cells have been
shown to communicate with each other via cytokine signaling during neovascularization. We previously demonstrated that interleukin-1β
(IL-1β) leads to induction of vascular endothelial growth factor (VEGF) in human colon carcinoma cells. As pericytes play
a role in regulating EC function, we hypothesized that IL-1β may mediate EC survival by induction of VEGF in a paracrine manner.
We investigated the effects of IL-1β on VEGF expression in human VSMCs (hVSMCs) and the signal transduction pathways that
may be involved. Treatment of hVSMCs with IL-1β induced VEGF expression in a time- and concentration-dependent manner and
increased both the VEGF promoter activity and the mRNA half-life. Treatment with IL-1β induced the expression of P38 mitogen-activated
protein kinase (MAPK) within 5 min but did not activate extracellular signal-regulated kinases (Erk)-1/2, c-jun amino terminal
kinase (JNK), or Akt. SB203580, a specific P38 MAPK inhibitor, blocked the ability of IL-1β to induce VEGF mRNA and promoter
activity. Conditioned media from hVSMCs pretreated with IL-1β prevented apoptosis of ECs, an effect that was partially abrogated
by VEGF-neutralizing antibodies. These data demonstrate that IL-1β may induce VEGF in hVSMCs, and suggest that this paracrine
signaling pathway, may prevent, in part, apoptosis of ECs.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
18.
KSHV LANA inhibits TGF-beta signaling through epigenetic silencing of the TGF-beta type II receptor 总被引:1,自引:0,他引:1
Signaling through the transforming growth factor–β (TGF-β) pathway results in growth inhibition and induction of apoptosis in various cell types. We show that this pathway is blocked in Kaposi sarcoma herpesvirus (KSHV)–infected primary effusion lymphoma through down-regulation of the TGF-β type II receptor (TβRII) by epigenetic mechanisms. Our data also suggest that KSHV infection may result in lower expression of TβRII in Kaposi sarcoma and multicentric Castleman disease. KSHV-encoded LANA associates with the promoter of TβRII and leads to its methylation and to the deacetylation of proximal histones. Reestablishment of signaling through this pathway reduces viability of these cells, inferring that KSHV-mediated blockage of TGF-β signaling plays a role in the establishment and progression of KSHV-associated neoplasia. These data suggest a mechanism whereby KSHV evades both the antiproliferative effects of TGF-β signaling by silencing TβRII gene expression and immune recognition by suppressing TGF-β–responsive immune cells through the elevated secretion of TGF-β1. 相似文献
19.
Cows' milk proteins cause similar Th1- and Th2-like immune response in diabetic and healthy children
Aims/hypothesis: Cows' milk proteins have been proposed to play a part in the pathogenesis of Type I (insulin-dependent) diabetes mellitus
but both epidemiological and immunological studies have given conflicting results. Thus we aimed to study the immunological
response to cows' milk proteins among diabetic and healthy children, focusing on the balance of Th1- and Th2-like lymphocytes.
Methods: Peripheral blood mononuclear cells from 30 Type I diabetic children (4 to 18 years old) were examined and compared with peripheral
blood mononuclear cells from 18 healthy age-matched control children (7 to 15 years old). Expression of IFN-γ and IL-4 mRNA were detected by realtime RT-PCR and as protein by ELISA after stimulation with BSA, the ABBOS-peptide (a.
a. 152–169) and β-lactoglobulin (βLG) from cows' milk and ovalbumin from hens' egg. Phytohaemagglutinin and keyhole limpet haemocyanin were used as positive
and negative controls, respectively.
Results: Bovine serum albumin caused a weak Th2-like response in Type I diabetic children, whereas BSA antibodies decreased with age
only among healthy children. Otherwise, cows' milk proteins (BSA, ABBOS and βLG) caused increased expression for IFN-γ and IL-4 mRNA in diabetic and healthy children. βLG caused the strongest immunological response, which decreased with age only among diabetic children. However, ovalbumin
from egg caused a similar activation of the immune system and the immune response was similar in both diabetic and healthy
children.
Conclusion/interpretation: Proteins from cows' milk caused an equal Th1- and Th2-like immune response in diabetic and healthy children. Thus, our results
do not support the hypothesis that cows' milk antigens are important for the immune process associated with Type I diabetes.
[Diabetologia (2001) 44: 1140–1147]
Received: 6 February 2001 and in revised form: 14 May 2001 相似文献
20.
Abstract
Aims/hypothesis. Interleukin-1β is a putative mediator of pancreatic beta-cell dysfunction and damage in Type I (insulin-dependent) diabetes mellitus. To
better understand the molecular mechanisms involved in IL-1β effects, we carried out a differential display of mRNA by RT-PCR to identify novel cytokine-regulated genes. Methods. Fluorescence activated cell sorting-purified rat pancreatic beta-cells were exposed for 6 or 24 h to IL-1β. Differentially expressed cDNA bands were cloned and then identified by comparing their sequences with data from the GenBank.
Differential gene expression was confirmed by RT-PCR using specific primers. Results. Interleukin-1β increased the expression of adenine nucleotide translocator-1, phospholipase D-1 and cytokine-induced neutrophil chemoattractant-1
and decreased expression of the protein tyrosine phosphatase-like protein IA-2. Interleukin-1β-induced differential expression of these genes in beta cells was confirmed by RT-PCR. In additional studies, IL-1β was shown to induce chemokines other than cytokine-induced neutrophil chemoattractant-1, including cytokine-induced neutrophil
chemoattractant-3 and monocyte chemotactic protein-1. Conclusion/interpretation. Our observations indicate that IL-1β modifies the expression of several genes in pancreatic beta cells. These genes may affect both function, viability and beta-cell
recognition by the immune system. Functional characterization of the mRNAs which have been identified could facilitate a better
understanding of the mechanisms leading to beta-cell destruction in Type I diabetes. [Diabetologia (1999) 42: 1199–1203]
Received: 4 June 1999 and in revised form: 1 July 1999 相似文献