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1.
Vasoactive peptides upregulate mRNA expression and secretion of vascular endothelial growth factor in human airway smooth muscle cells 总被引:2,自引:0,他引:2
Alagappan VK Willems-Widyastuti A Seynhaeve AL Garrelds IM ten Hagen TL Saxena PR Sharma HS 《Cell biochemistry and biophysics》2007,47(1):109-118
Airway remodeling and associated angiogenesis are documented features of asthma, of which the molecular mechanisms are not
fully understood. Angiotensin (ANG)II and endothelin (ET)-1 are potent vasoconstricting circulatory hormones implicated in
asthma. We investigated the effects of ANG II and ET-1 on human airway smooth muscle (ASM) cells proliferation and growth
and examined the mRNA expression and release of the angiogenic peptide, vascular endothelial growth factor (VEGF). Serum deprived
(48 h) human ASM cells were incubated with ANG II (100 nM) or ET-1 (10nM) for 30 min, 1, 2, 4, 8, 16, and 24 h and the endogenous synthesis of VEGF was examined in relation to control cells receiving
serum free culture medium. ET-1 induced time dependent DNA biosynthesis as determined by [3H]-thymidine incorporation assay. Using northern blot hybridization, we detected two mRNA species of 3.9 and 1.7 kb encoding
VEGF in the cultured smooth muscle cells. Both ANG II and ET-1 induced the mRNA expression (two-to threefold) and secretion
(1.8-to 2.8-fold) of VEGF reaching maximal levels between 4–8 h of incubation. Induced expression and release of VEGF declined
after 8 h of ANG II incubation while levels remained elevated in the case of ET-1. The conditioned medium derived from ET-1-treated
ASM cells induced [3H]-thymidine incorporation and cell number in porcine pulmonary artery endothelial as well as human umbilical vein endothelial
cells. Moreover, the VEGF tyrosine kinase receptor inhibitor blocked the conditioned medium induced mitogenesis in endothelial
cells. Our results suggest a potential role for ANG II and ET-1 in ASM cell growth and upregulation of VEGF that may participate
in endothelial cell proliferation via paracrine mechanisms and thus causing pathological angiogenesis and vascular remodelling
seen during asthma. 相似文献
2.
3.
Huang CD Ammit AJ Tliba O Kuo HP Penn RB Panettieri RA Amrani Y 《Journal of biomedical science》2005,12(5):763-776
Summary Using thapsigargin (Tg), an agent that mobilizes calcium by directly emptying intracellular stores, we previously showed that
intracellular calcium may play an important role in the regulation of intercellular adhesion molecule (ICAM)-1 gene expression
induced by cytokines in human airway smooth muscle (ASM) cells. In the present study, we extended this previous observation
by comparing the effect of Tg and other calcium-mobilizing G-protein-coupled receptor (GPCR) agonists on the expression of
different pro-inflammatory genes in response to tumor necrosis factor (TNF)-α in ASM cells. We found that in resting cells,
Tg (10–100 nM) or the bradykinin (BK) (1–10 μM) and thrombin (Thr) (1 U/ml) stimulated interleukin (IL)-6 secretion but had
no effect on regulated on activation, normal T cells expressed and secreted (RANTES) levels. More importantly, such calcium-mobilizing
agents significantly enhanced TNF-α-induced IL-6 secretion while RANTES secretion was abrogated. The use of luciferase-tagged
IL-6 and RANTES promoter constructs demonstrated similar effects of Tg on IL-6 and RANTES genes in basal and TNF-α-stimulated
conditions. The cyclic adenosine monophosphate (cAMP)-dependent pathway plays a minor role in this differential regulation
of IL-6 and RANTES genes expression. 2-Aminoethoxydiphenyl borate (APB), a blocker of store-operated calcium channels (SOCs),
and bisindolylmaleimide I (Bis I), a broad-spectrum protein kinase C (PKC) inhibitor, inhibited the basal and synergic effects
of IL-6 secretion in response to calcium-mobilizing agents and TNF-α, but did not prevent the abrogated effect of RANTES secretion.
We also found that Go-6976, a selective calcium-dependent PKC isozyme inhibitor, did not inhibit IL-6 secretion in response
to GPCR agonist and TNF-α; whereas Rottlerlin, a PKC-δ inhibitor, inhibited both Thr- and TNF-α-induced expression of IL-6,
while BK-induced IL-6 secretion was not affected. Interestingly, TNF-α-induced interferon regulatory factor (IRF)-1 activation
was significantly inhibited by all calcium-mobilizing agents, BK, Thr and Tg. These results show that calcium-mobilizing GPCR
agonists functionally interact with TNF-α to differentially regulate pro-inflammatory genes expression in human ASM cells,
possibly by involving Tg-sensitive intracellular calcium stores, SOC and PKC. 相似文献
4.
Kazi AS Lotfi S Goncharova EA Tliba O Amrani Y Krymskaya VP Lazaar AL 《American journal of physiology. Lung cellular and molecular physiology》2004,286(3):L539-L545
In severe asthma, cytokines and growth factors contribute to the proliferation of smooth muscle cells and blood vessels, and to the increased extracellular matrix deposition that constitutes the process of airway remodeling. Vascular endothelial growth factor (VEGF), which regulates vascular permeability and angiogenesis, also modulates the function of nonendothelial cell types. In this study, we demonstrate that VEGF induces fibronectin secretion by human airway smooth muscle (ASM) cells. In addition, stimulation of ASM with VEGF activates ERK, but not p38MAPK, and fibronectin secretion is ERK dependent. Both ERK activation and fibronectin secretion appear to be mediated through the VEGF receptor flt-1, as evidenced by the effects of the flt-1-specific ligand placenta growth factor. Finally, we demonstrate that ASM cells constitutively secrete VEGF, which is increased in response to PDGF, transforming growth factor-beta, IL-1beta, and PGE(2). We conclude that ASM-derived VEGF, through modulation of the extracellular matrix, may play an important role in airway remodeling seen in asthma. 相似文献
5.
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
6.
Role of extracellular matrix and its regulators in human airway smooth muscle biology 总被引:3,自引:0,他引:3
Parameswaran K Willems-Widyastuti A Alagappan VK Radford K Kranenburg AR Sharma HS 《Cell biochemistry and biophysics》2006,44(1):139-146
Altered extracellular matrix (ECM) deposition contributing to airway wall remodeling is an important feature of asthma and
chronic obstructive pulmonary disease (COPD). The molecular mechanisms of this process are poorly understood. One of the key
pathological features of these diseases is thickening of airway walls. This thickening is largely to the result of airway
smooth muscle (ASM) cell hyperplasia and hypertrophy as well as increased deposition of ECM proteins such as collagens, elastin,
laminin, and proteoglycans around the smooth muscle. Many growth factors and cytokines, including fibroblast growth factor
(FGF)-1, FGF-2, and transforming growth factor (TGF)-α1, that are released from the airway wall have the potential to contribute to airway remodeling, revealed by enhanced ASM proliferation
and increased ECM protein deposition. TGF-α1 and FGF-1 stimulate mRNA expression of collagen I and III in ASM cells, suggesting their role in the deposition of extracellular
matrix proteins by ASM cells in the airways of patients with chronic lung diseases. Focus is now on the bidirectional relationship
between ASM cells and the ECM. In addition to increased synthesis of ECM proteins, ASM cells can be involved in downregulation
of matrix metalloproteinases (MMPs) and upregulation of tissue inhibitors of metalloproteinases (TIMPs), thus eventually contributing
to the alteration in ECM. In turn, ECM proteins promote the survival, proliferation, cytokine synthesis, migration, and contraction
of human airway smooth muscle cells. Thus, the intertwined relationship of ASM and ECM and their response to stimuli such
as chronic inflammation in diseases such as asthma and COPD contribute to the remodeling seen in airways of patients with
these diseases. 相似文献
7.
G. van Luijtelaar S. Lyashenko R. Vastyanov G. Verbeek A. Oleinik C. van Rijn G. Volokhova A. Shandra A. Coenen L. Godlevsky 《Neurophysiology》2012,43(6):478-486
We investigated the role of two cytokines, IL-1β and TNF-α, in the development of absence seizures using a genetic model of
absence epilepsy in WAG/Rij rats. We administered these cytokines to animals systemically and measured the number of spike-wave
discharges (SWDs) in the EEG. We also coadministered IL-1β with the GABA reuptake inhibitor tiagabine and measured the levels
of IL-1β and TNF-α in the brain and blood plasma of 2-, 4-, and 6-month-old WAG/Rij rats and animals that served as a non-epileptic
control (ACI). We found that IL-1β induced a significant increase in SWDs 2-5 h after administration, while TNF-α enhanced
SWDs much later. Both cytokines enhanced passive behavior; body temperature was elevated only after TNF-α. The action of tiagabine
was potentiated by earlier IL-1β injection, even when IL-1β was no longer active. Young WAG/Rij rats showed higher levels
of TNF-α in blood serum than young ACI rats; the effects in the brain tended to be opposite. The marked differences in timing
of the increase in SWDs suggest different time scales for the action of both cytokines tested. It is proposed that the results
found after TNF-α are due to the de novo synthesis of IL-1β. TNF-α may possess neuroprotective effects. IL-1β might increase GABA-ergic neurotransmission. The changes
in the efficacy of antiepileptic drugs related to changes in the cytokine systems may have some clinical relevance. 相似文献
8.
Mast cell (MC) activation in the rheumatoid lesion provides numerous mediators that contribute to inflammatory and degradative processes, especially at sites of cartilage erosion. MC activation in rheumatoid synovial tissue has often been associated with tumour necrosis factor (TNF)-α and interleukin (IL)-1β production by adjacent cell types. By contrast, our in situ and in vitro studies have shown that the production of IL-15 was independent of MC activation, and was not related to TNF-α and IL-1β expression. Primary cultures of dissociated rheumatoid synovial cells produced all three proinflammatory cytokines, with production of IL-1β exceeding that of TNF-α, which in turn exceeded that of IL-15. In vitro cultures of synovial macrophages, synovial fibroblasts and articular chondrocytes all produced detectable amounts of free IL-15, macrophages being the most effective. 相似文献
9.
In this study, the levels of TNF-α and its soluble receptors sTNF-Rp55 and sTNF-Rp75 were analyzed in cocultures of human
colon carcinoma cell spheroids prepared from different grades of tumors with normal human colon epithelium, myofibroblast,
and endothelial cell monolayers. Additionally, the influence of exogenously added rhTGF-β1 (2 ng/ml) on the TNF-α and sTNF-Rs
levels was tested. Direct interactions of colon carcinoma spheroids with normal cells caused decreases in TNF-α levels and
normal cell-dependent changes in sTNF-Rs amounts as compared to normal cells cultured alone. The addition of rhTGF-β1 to the
cocultures caused a significant increase in TNF-α levels with a simultaneous decrease in the amounts of both sTNF-Rs. During
direct interactions of colon carcinoma cells with normal tissue, paracrine effects are very important. We showed that TGF-β1
acts synergistically with TNF-α and significantly limits sTNF-Rs shedding. Therefore, TNF-Rs bound to cellular membranes,
but not their soluble forms, play an important role in tumor/normal cell interactions. TGF-β1 and sTNF-Rs, in turn, may be
valuable factors in colon cancer development and metastasis. 相似文献
10.
11.
Vijay K. T. Alagappan Willem I. de Boer Virendra K. Misra Wolter J. Mooi Hari S. Sharma 《Cell biochemistry and biophysics》2013,67(2):219-234
Asthma and chronic obstructive pulmonary disease remain a global health problem, with increasing morbidity and mortality. Despite differences in the causal agents, both diseases exhibit various degrees of inflammatory changes, structural alterations of the airways leading to airflow limitation. The existence of transient disease phenotypes which overlap both diseases and which progressively decline the lung function has complicated the search for an effective therapy. Important characteristics of chronic airway diseases include airway and vascular remodeling, of which the molecular mechanisms are complex and poorly understood. Recently, we and others have shown that airway smooth muscle (ASM) cells are not only structural and contractile components of airways, rather they bear capabilities of producing large number of pro-inflammatory and mitogenic factors. Increase in size and number of blood vessels both inside and outside the smooth muscle layer as well as hyperemia of bronchial vasculature are contributing factors in airway wall remodeling in patients with chronic airway diseases, proposing for the ongoing mechanisms like angiogenesis and vascular dilatation. We believe that vascular changes directly add to the airway narrowing and hyper-responsiveness by exudation and transudation of proinflammatory mediators, cytokines and growth factors; facilitating trafficking of inflammatory cells; causing oedema of the airway wall and promoting ASM accumulation. One of the key regulators of angiogenesis, vascular endothelial growth factor in concerted action with other endothelial mitogens play pivotal role in regulating bronchial angiogenesis. In this review article we address recent advances in pulmonary angiogenesis and remodelling that contribute in the pathogenesis of chronic airway diseases. 相似文献
12.
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
13.
Preciado-Patt Liana Cahalon Liora Hershkovitz Rami Lider Ofer Pras Mordechai Fridkin Mati 《International journal of peptide research and therapeutics》1998,5(5-6):349-355
Summary Serum amyloid A (SAA), an acute-phase reactant, exists naturally as a minor protein in the sera of healthy individuals. However,
its levels in sera are increased markedly during various transient and chronic inflammatory diseases, often concomitantly
with accumulation at inflicted sites. SAA is synthesized mainly in the liver following the synergistic action of cytokines,
mainly tumor necrosis factor-α (TNF-α) and interleukin-1 and-6 (IL-1 and IL-6). It was already shown by us that upon interaction
with SAA or amyloid A (AA), the extracellular matrix (ECM) and laminin induced the adhesion of resting human CD4+ T-cells in an apparently β1-integrin-mediated manner. Herein we have shown that the SAA-ECM complex modulates the regulation of cytokine synthesis by
human T-lymphocytes. The SAA-ECM complex dramatically enhanced the release of TNF-α by human T-cells in a dose-dependent manner,
reaching its maximal effect in the presence of 100 μM recombinant SAA. The SAA domain, responsible for the enhanced release
of TNF-α by human T-lymphocytes, is apparently the amyloid A protein (AA, i.e. SAA2-82). Specifically, TNF-α enhanced secretion
is mediated through intimate interactions of SAA/AA, with laminin. Thus, the ECM serving as a temporary anchorage site for
SAA and AA seems to be involved in regulating TNF-α secretion and the recruitment and accumulation of immunocytes in extravascular,
inflammatory compartments. 相似文献
14.
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
15.
16.
We have previously shown that oral administration of skimmed milk(SM) fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1/SM) to DBA/1 mice inhibited the development of collagen-induced arthritis (CIA). In this study, our
aim was to examine possible mechanisms of inhibiting the development of CIA. We studied the effect of OLL1073R-1/SM on cytokine
secretion from cells of popliteal lymph nodes (lymph node cells; LNC) of mice. The results showed that feeding OLL1073R-1/SM
inhibited secretion of proinflammatory cytokines such as interferon γ (IFN-γ), interleukin 6 (IL-6), tumor necrosis factor
α (TNF-α) and the chemokine, monocyte chemoattractant protein 1 (MCP-1). The most prominent effect was inhibition of TNF-α.
Secretion of IL-2 and IL-4 were not influenced. Feeding OLL1073R-1/SM inhibited secretion of proinflammatory cytokines produced
by accessory cells, but not T cells. We conclude that CIA may be prevented via down regulation of secretion of proinflammatory
cytokines such as IL-6, TNF-α and IFN-γ, and of the chemokine of MCP-1.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
17.
18.
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
19.
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
20.
Johanna Westra Berber Doornbos-van der Meer Peter de Boer Miek A van Leeuwen Martin H van Rijswijk Pieter C Limburg 《Arthritis research & therapy》2004,6(4):R384
In inflammatory processes, the p38 mitogen-activated protein kinase (MAPK) signal transduction route regulates production
and expression of cytokines and other inflammatory mediators. Tumor necrosis factor α (TNF-α) is a pivotal cytokine in rheumatoid
arthritis and its production in macrophages is under control of the p38 MAPK route. Inhibition of the p38 MAPK route may inhibit
production not only of TNF-α, but also of other inflammatory mediators produced by macrophages, and indirectly of inflammatory
mediators by other cells induced by TNF-α stimulation. Here we investigate the effects of RWJ 67657, a p38 MAPK inhibitor,
on mRNA expression and protein production of TNF-α and other inflammatory mediators, in monocyte-derived macrophages. A strong
inhibition of TNF-α was seen at pharmacologically relevant concentrations of RWJ 67657, but also inhibition of mRNA expression
of IL-1β, IL-8, and cyclooxygenase-2 was shown. Furthermore, it was shown that monocyte-derived macrophages have a high constitutive
production of matrix metalloproteinase 9, which is not affected by p38 MAPK inhibition. The results presented here may have
important implications for the treatment of rheumatoid arthritis. 相似文献