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1.
Introduction
Epigallocatechin-3-gallate (EGCG) is a bioactive polyphenol of green tea and exerts potent anti-inflammatory effects by inhibiting signaling events and gene expression. Interleukin-1beta (IL-1β) is the principal cytokine linked to cartilage degradation in osteoarthritis (OA). The objective of this study was to evaluate the global effect of EGCG on IL-1β-induced expression of proteins associated with OA pathogenesis in human chondrocytes. 相似文献2.
Rowan S Hardy Andrew Filer Mark S Cooper Greg Parsonage Karim Raza Debbie L Hardie Elizabeth H Rabbitt Paul M Stewart Christopher D Buckley Martin Hewison 《Arthritis research & therapy》2006,8(4):R108-10
Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation.
We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of
the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Expression, activity and function of 11β-HSD1 was assessed
in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid
arthritis or osteoarthritis. 11β-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were
higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative
to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis
factor-α or IL-1β (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4-fold and 14-fold;
synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-γ was without effect, and there was no difference in 11β-HSD1
expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the
presence of 100 nmol/l cortisone, IL-6 production – a characteristic feature of synovial derived fibroblasts – was significantly
reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11β-HSD inhibitor,
emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences
in fibroblast-derived glucocorticoid production (via the enzyme 11β-HSD1) between cells from distinct anatomical locations
may play a key role in the predeliction of certain tissues to develop persistent inflammation. 相似文献
3.
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
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Wähämaa H Schierbeck H Hreggvidsdottir HS Palmblad K Aveberger AC Andersson U Harris HE 《Arthritis research & therapy》2011,13(4):R136
Introduction
In addition to its direct proinflammatory activity, extracellular high mobility group box protein 1 (HMGB1) can strongly enhance the cytokine response evoked by other proinflammatory molecules, such as lipopolysaccharide (LPS), CpG-DNA and IL-1β, through the formation of complexes. Extracellular HMGB1 is abundant in arthritic joint tissue where it is suggested to promote inflammation as intra-articular injections of HMGB1 induce synovitis in mice and HMGB1 neutralizing therapy suppresses development of experimental arthritis. The aim of this study was to determine whether HMGB1 in complex with LPS, interleukin (IL)-1α or IL-1β has enhancing effects on the production of proinflammatory mediators by rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF). Furthermore, we examined the toll-like receptor (TLR) 4 and IL-1RI requirement for the cytokine-enhancing effects of the investigated HMGB1-ligand complexes. 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
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Isabel García-Arnandis Maria Isabel Guillén Francisco Gomar Jean-Pierre Pelletier Johanne Martel-Pelletier Maria José Alcaraz 《Arthritis research & therapy》2010,12(4):R165
Introduction
High mobility group box 1 (HMGB1) is released by necrotic cells or secreted in response to inflammatory stimuli. Extracellular HMGB1 may act as a pro-inflammatory cytokine in rheumatoid arthritis. We have recently reported that HMGB1 is released by osteoarthritic synoviocytes after activation with interleukin-1beta (IL-1β) The present study investigated the role of HMGB1 in synovial inflammation in osteoarthritis (OA). 相似文献10.
Birk Poller Jürgen Drewe Stephan Krähenbühl Jörg Huwyler Heike Gutmann 《Cellular and molecular neurobiology》2010,30(1):63-70
Brain capillary endothelial cells form the blood–brain barrier (BBB), a highly selective permeability membrane between the
blood and the brain. Besides tight junctions that prevent small hydrophilic compounds from passive diffusion into the brain
tissue, the endothelial cells express different families of drug efflux transport proteins that limit the amount of substances
penetrating the brain. Two prominent efflux transporters are the breast cancer resistance protein and P-glycoprotein (P-gp).
During inflammatory reactions, which can be associated with an altered BBB, pro-inflammatory cytokines are present in the
systemic circulation. We, therefore, investigated the effect of the pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6
(IL-6) and tumor necrosis factor-α (TNF-α) on the expression and activity of BCRP and P-gp in the human hCMEC/D3 cell line.
BCRP mRNA levels were significantly reduced by IL-1β, IL-6 and TNF-α. The strongest BCRP suppression at the protein level
was observed after IL-1β treatment. IL-1β, IL-6 and TNF-α also significantly reduced the BCRP activity as assessed by mitoxantrone
uptake experiments. P-gp mRNA levels were slightly reduced by IL-6, but significantly increased after TNF-α treatment. TNF-α
also increased protein expression of P-gp but the uptake of the P-gp substrate rhodamine 123 was not affected by any of the
cytokines. This in vitro study indicates that expression levels and activity of BCRP, and P-gp at the BBB may be altered by
acute inflammation, possibly affecting the penetration of their substrates into the brain. 相似文献
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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
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Farshad Malihi Azadeh Hosseini-Tabatabaei Hadi Esmaily Reza Khorasani Maryam Baeeri Mohammad Abdollahi 《Central European Journal of Biology》2009,4(3):369-380
Type 1 diabetes mellitus (T1DM) is characterized by an impairment of the insulin-secreting beta cells with an immunologic
base. Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and free radicals are believed
to play key roles in destruction of pancreatic β cells. The present study was designed to investigate the effect of Silybum marianum seed extract (silymarin), a combination of several flavonolignans with immunomodulatory, anti-oxidant, and anti-inflammatory
potential on streptozotocin (STZ)-induced T1DM in mouse. Experimental T1DM was induced in male albino mice by IV injection
of multiplelow- doses of STZ for 5 days. Seventy-two male mice in separate groups received various doses of silymarin (20,
40, and 80 mg/kg) concomitant or after induction of diabetes for 21 days. Blood glucose and pancreatic biomarkers of inflammation
and toxic stress (IL-1β, TNF-α, myeloperoxidase, lipid peroxidation, protein oxidation, thiol molecules, and total antioxidant
capacity) were determined. Silymarin treatment reduced levels of inflammatory cytokines such as TNF-α and IL-1β and oxidative
stress mediators like myeloperoxidase activity, lipid peroxidation, carbonyl and thiol content of pancreatic tissue in an
almost dose dependent manner. No marked difference between the prevention of T1DM and the reversion of this disease by silymarin
was found. Use of silymarin seems to be helpful in T1DM when used as pretreatment or treatment. Benefit of silymarin in human
T1DM remains to be elucidated by clinical trials. 相似文献
15.
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
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Interleukin-1β enhances the effect of serum deprivation on rat annular cell apoptosis 总被引:3,自引:0,他引:3
Zhao CQ Liu D Li H Jiang LS Dai LY 《Apoptosis : an international journal on programmed cell death》2007,12(12):2155-2161
Excessive apoptosis of disc cells is believed to play an important role in intervertebral disc (IVD) degeneration. It has
been shown that interleukin-1β (IL-1β) is involved in the failure of disc matrix by suppressing the synthesis of matrix components
and stimulating the expression of matrix metalloproteinases. However, whether IL-1β induces disc cell apoptosis is still unclear.
The objective of this study was to investigate the effect of IL-1β on the apoptosis of rat annular cells cultured with or
without serum supplement. First-passage rat annular cells were cultured with 0% or 10% fetal bovine serum (FBS) supplement
and stimulated with 0, 10, 20 or 50 ng/ml IL-1β for 12, 24 or 48 h. Apoptotic incidences were quantified by flow cytometry,
morphologic changes in apoptotic cells were visualized by Hoechst 33258 staining and phase-contrast microscopy, and caspase-3
activity was also determined. When rat annular cells were cultured with 10% FBS supplement, no significant changes in apoptotic
incidences, apoptotic morphology and caspase-3 activity were observed even when cells were stimulated with 50 ng/ml IL-1β
for 48 h. In contrast, serum deprivation for 24 h led to an increase in apoptotic incidences, the number of apoptotic nuclei
and caspase-3 activity, and IL-1β significantly increased the effects of serum deprivation in a dose-dependent manner. Our
results indicate that IL-1β alone is not a sufficient stimulus to induce disc cell apoptosis and that in order to suppress
disc cell apoptosis, improving the nutrient supply to the disc may be more effective than antagonizing the adverse effects
of IL-1β. 相似文献
18.
Padró M Mejías-Luque R Cobler L Garrido M Pérez-Garay M Puig S Peracaula R de Bolós C 《Glycoconjugate journal》2011,28(2):99-110
Inflammation of stomach mucosa has been postulated as initiator of gastric carcinogenesis and the presence of pro-inflammatory
cytokines can regulate specific genes involved in this process. The cellular expression pattern of glycosyltransferases and
Lewis antigens detected in the normal mucosa changed during the neoplassic transformation. The aim of this work was to determine
the regulation of specific fucosyltransferases and sialyltransferases by IL-1β and IL-6 pro-inflammatory cytokines in MKN45
gastric cancer cells. IL-1β induced significant increases in the mRNA levels of FUT1, FUT2 and FUT4, and decreases of FUT3
and FUT5. In IL-6 treatments, enhanced FUT1 and lower FUT3 and FUT5 mRNA expression were detected. No substantial changes
were observed in the levels of ST3GalIII and ST3GalIV. The activation of FUT1, FUT2 and FUT4 by IL-1β is through the NF-κB
pathway and the down-regulation of FUT3 and FUT5 by IL-6 is through the gp130/STAT-3 pathway, since they are inhibited specifically
by panepoxydone and AG490, respectively. The levels of Lewis antigens after IL-1β or IL-6 stimulation decreased for sialyl-Lewis
x, and no significant differences were found in the rest of the Lewis antigens analyzed, as it was also observed in subcutaneous
mice tumors from MKN45 cells treated with IL-1β or IL-6. In addition, in 61 human intestinal-type gastric tumors, sialyl-Lewis
x was highly detected in samples from patients that developed metastasis. These results indicate that the expression of the
fucosyltransferases involved in the synthesis of Lewis antigens in gastric cancer cells can be specifically modulated by IL-1β
and IL-6 inflammatory cytokines. 相似文献
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20.
Yves Chicheportiche Rachel Chicheportiche Irene Sizing Jeff Thompson Christopher B Benjamin Christine Ambrose Jean-Michel Dayer 《Arthritis research & therapy》2001,4(2):126-8
Human tumour necrosis factor (TNF)-like weak inducer of apoptosis (hTWEAK) and two anti-hTWEAK mAbs were tested for their ability to elicit or block inflammatory responses in cultured human dermal fibroblasts and synoviocytes. Incubation with hTWEAK increased the production of prostaglandin E2, matrix metalloproteinase-1 (MMP-1), IL-6, and the chemokines IL-8, RANTES (regulated on activation, normal T expressed and secreted) and interferon-γ-inducible protein-10 (IP-10) in culture supernatant of fibroblasts and synoviocytes. In combination with TNF or IL-1β, hTWEAK further stimulated the secretion of prostaglandin E2, MMP-1, IL-6 and IL-8 up to fourfold, and IP-10 and RANTES up to 70-fold compared to TNF or IL-1β alone. An anti-hTWEAK mAb, BCB10, blocked the effects of hTWEAK, whereas hTWEAK crosslinked by the anti-hTWEAK mAb, BEB3, further stimulated the inflammatory response of fibroblasts and synoviocytes. The anti-hTWEAK mAbs were ineffective in blocking or increasing the responses of TNF or IL-1β and blocking anti-TNF mAb was ineffective in preventing the responses to TWEAK. These results were also confirmed at the RNA level for MMP-1, macrophage chemoattractant protein-1, RANTES, macrophage inflammatory protein-1α, IP-10 and IL-8. TWEAK in synergism with IL-1 and TNF may be an additional cytokine that plays a role in destructive chronic arthritic diseases. 相似文献