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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biosynthesis of apolipoprotein (apo) E has been previously demonstrated to be regulated in macrophages by intracellular free cholesterol levels as well as by macrophage activating factors. In this report, the regulation of apo E secretion by cytokines detected within atherosclerotic lesions has been investigated. Granulocyte macrophage-colony stimulating factor (GM-CSF) stimulated macrophages had a 3-5-fold reduction in apo E secretion, comparable to that observed for gamma interferon (IFN gamma), while tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) resulted in a 2-fold decrease. In contrast to the reduction in apo E secretion by these cytokines, transforming growth factor beta (TGF-beta) stimulated macrophages secreted 3-fold greater amounts of apo E than controls. The reduced secretion of apo E by GM-CSF was reversible, heat labile, dose dependent, maximal 48 h after cytokine exposure and was coincident with an increase in fibronectin secretion. The opposing effects of GM-CSF and TGF-beta on apo E secretion were consistent with similar changes detected in apo E mRNA levels. Cytokine effects on apo E secretion in cholesterol loaded macrophages were also investigated and found to be similar to the non-loaded cells with GM-CSF decreasing and TGF-beta increasing apo E secretion. The observed differences in apo E secretion did not correlate with any significant changes in either cellular cholesterol distribution in the non-cholesterol loaded macrophages or in basal ACAT activity. In addition to changes in apo E secretion, cytokine treated macrophages pulsed with [14C]oleate and acetylated LDL for 2-6 h had a 2-fold increase (GM-CSF) or decrease (TGF-beta) in cholesterol esterification. Therefore, GM-CSF and TGF-beta mediated changes in apo E secretion may occur through a mechanism independent of changes in cellular free cholesterol levels. These results suggest that cytokines expressed within an atheroma may play an important role in the modulation of macrophage mediated reverse cholesterol transport.
Atherosclerosis 1992 Oct
PMID:Cytokine regulation of macrophage apo E secretion: opposing effects of GM-CSF and TGF-beta. 146 52

Monokines, including tumor necrosis factor alpha (TNF-alpha), have been implicated in the pathogenesis of several pathologic processes, including atherosclerosis. Because estrogen has been found to offer a certain degree of protection against atherosclerotic progression, we examined the effect of estrogen on the expression of TNF-alpha mRNA in a monocyte-macrophage cell line, THP-1. Cells were exposed to 12-O-tetradecanoylphorbol 13-acetate (TPA, 50 ng/ml) for 48 or 96 h to induce differentiation. Some of the cells were treated with lipopolysaccharide (LPS, 10 micrograms/ml) in the last 3 h and/or ethinyl estradiol (estrogen, 10(-9) M) in the last 20 h. Total cellular RNA was isolated and cDNA synthesized and than coamplified using the polymerase chain reaction (PCR) in the presence of two sets (pairs) of 32P-labeled primers, one for TNF-alpha (product size 325 bp) and the second for the internal control, glyceraldehyde 3-phosphate dehydrogenase (G3PDH; 983 bp). The resultant PCR products were separated by agarose gel electrophoresis, and the ratios of radioactivity incorporated into TNF-alpha PCR products to G3PDH products were used to assess the relative changes in the levels of TNF-alpha mRNA abundance in response to various substances. Treatment with TPA for 48 h induced the expression of TNF-alpha mRNA. Treatment of these TPA-stimulated cells with estrogen caused a 62% decrease in TNF-alpha message abundance (p < 0.01). Similar results were obtained with cells stimulated with TPA for 96 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Lymphokine Cytokine Res 1994 Dec
PMID:Estrogen modulates the expression of tumor necrosis factor alpha mRNA in phorbol ester-stimulated human monocytic THP-1 cells. 770 11

The importance of the immuno-inflammatory processes involved in the pathogenesis of atherosclerosis has been reconsidered since the various cellular components of the atherosclerotic plaque were more precisely characterized. Macrophages and T lymphocytes, as well as endothelial and smooth muscle cells are involved in the formation of the fibrolipidic lesion. This is suggestive of a delayed-type hypersensitivity reaction, with oxidized low-density lipoproteins (LDL) as possible antigenic stimulus. Cytokines, which are mediators of the immuno-inflammatory response, are locally expressed in the atherosclerotic plaque; they coordinate cell interactions and modulate the functions of vascular cells.
Eur Cytokine Netw
PMID:Cytokines, immuno-inflammatory response and atherosclerosis. 794 63

Contribution of endothelial cells to normal immune processes (circulation of leukocytes, immune diapedesis, presentation of antigens) as well as to pathology caused by viral diseases is described. Cytokine secretion and expression of adhesion molecules, particularly during viral infections are described. Permissiveness of endothelial cells to HIV infection is presented. Contribution of herpesviruses (CMV, HSV) to thrombosis and atherosclerosis is also considered.
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PMID:[Contribution of endothelial cells to the immune processes. Influence of viral infections]. 797

Factors controlling the proliferation of vascular smooth muscle cells (SMC) are thought to be key elements in the progression of atherosclerosis. We have previously shown that interleukin 6 (IL-6) stimulates the growth of SMC in vitro and that IL-6 gene transcripts are expressed in atherosclerotic lesions of genetically hyperlipidemic rabbits. To understand the involvement of IL-6 in the development of human atherosclerosis, we investigated IL-6 mRNA expression in atherosclerotic arteries from patients undergoing surgical vascularization, utilizing reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization analyses. In RT-PCR analysis, the atherosclerotic arteries showed 10- to 40-fold levels of IL-6 mRNA expression over the non-atherosclerotic artery. In in situ hybridization analysis, IL-6 gene transcripts were observed in the thickened intimal layer of atherosclerotic lesions. These results strongly suggest the involvement of IL-6 in the development of human atherosclerosis.
Cytokine 1994 Jan
PMID:Interleukin 6 gene transcripts are expressed in human atherosclerotic lesions. 800 39

Monokines, such as interleukin-1, have been implicated in the pathogenesis of several pathologic processes, including the initiation and progression of atherosclerosis. Since estrogen has been identified as a modulator of atherosclerosis progression, we sought to examine the effect of estrogen on the inducible expression of interleukin-1 beta (IL-1 beta) and interleukin-1 alpha (IL-1 alpha) mRNA in the monocytic cell line, THP-1. Cells were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) (50 ng/ml) for 48 or 96 h to induce differentiation. Some cells were treated with lipopolysaccharide (LPS) (10 micrograms/ml) in the last 3 h and/or 10(-9) M ethinyl estradiol (estrogen) in the last 20 h. Total cellular RNA was isolated, and cDNA was synthesized and amplified using the polymerase chain reaction (PCR) using two sets (pairs) of 32P-labeled primers, one for IL-1 beta (product size 388 bp) and the second for the internal control, beta-actin (1126 bp), or to detect another cytokine mRNA, a set of primers for IL-1 alpha (product size 420 bp) and beta-actin. The PCR products were separated on a 3.0% agarose gel and the ratio of radioactivity incorporated into cytokine PCR products and beta-actin products was determined to assess the relative changes in the relative levels of cytokine to beta-actin mRNA abundance in response to various inducers. Treatment with TPA for 48 h induced expression of IL-1 beta mRNA, an effect that was enhanced two fold by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)
Lymphokine Cytokine Res 1994 Feb
PMID:The inducible expression of THP-1 cell interleukin-1 mRNA: effects of estrogen on differential response to phorbol ester and lipopolysaccharide. 818 19

In the present study the effect of replacement of dietary fat by palm oil in the normal Western diet on the in vitro release of the inflammatory cytokines tumour necrosis factor (TNF), interleukin (IL)-6 and IL-8 was examined. A maximal replacement of 700 g/kg dietary fat was achieved for thirty-eight male volunteers who consumed either a palm-oil diet or a control diet in a double-blind, cross-over study with 6-week experimental periods, and 3-week run-in and wash-out periods. At the end of both experimental periods, whole blood was stimulated in vitro with 0.02 (sub-optimal), or 10 ng lipopolysaccharide (LPS)/ml (maximal), whereafter TNF, IL-6, and IL-8 concentrations in the culture supernatant fraction were measured using specific enzyme-linked immunosorbent assays (ELISA). Mean cytokine production with sub-optimal, or maximal LPS stimulation of peripheral whole blood was similar for both the palm oil, and the control group. The relative TNF response, however, was reduced by replacement of dietary fat with palm oil. Separate analysis of the data from the first and second experimental periods strongly suggested that the residual effect of the palm-oil diet on the relative TNF response was longer than 9 weeks. Cytokine homeostasis determines the course of the inflammatory response and the progression of atherosclerosis. The effect of palm-oil consumption on the proneness of the peripheral blood cells to produce TNF may, therefore, alter the prevalence of these common diseases.
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PMID:The effect of replacement of dietary fat by palm oil on in vitro cytokine release. 845 24

We investigated monocyte chemoattractant protein-1 (MCP-1) mRNA expression in rat vascular smooth muscle cells (VSMC) and in human atherosclerotic arteries to test the involvement of MCP-1 in the pathogenesis of atherosclerosis. In Northern blot analysis, MCP-1 mRNA expression was not observed in unstimulated cultured rat vascular smooth muscle cells (VSMC), but its expression was clearly observed by exposure to tumour necrosis factor-alpha (100 U/ml) for 2-6 h. Mitogen-activated protein kinase activity in VSMC incubated in serum-free culture medium was increased by exposure to 0.5% fetal bovine serum, while the effect was significantly suppressed in the presence of MCP-1 (100 ng/ml). We then evaluated MCP-1 mRNA expression in atherosclerotic arteries obtained from 12 patients undergoing bypass revascularization through reverse transcription-polymerase chain reaction analysis and observed MCP-1 mRNA expression in all atherosclerotic arteries studied. These results support the premise that MCP-1 is secreted by VSMC in atherosclerotic plaques as well as by endothelial cells and macrophages and contributes to the pathogenesis of atherosclerosis.
Cytokine 1995 Aug
PMID:Expression of monocyte chemoattractant protein-1 in vascular tissue. 858 Mar 75

Cytokines are pleiotropic mediators of inflammation and immunity. Leukocytes and vascular cells are both sources of cytokines and targets for them. Several cytokines affect key functions of vascular wall cells. Several clinical acute or chronic inflammatory situations associate modifications of the cytokine network and a prothrombotic state. Many experimental data support the hypothesis that endothelial cells have an active role in these situations. Endothelial cells activated by cytokines such as tumor necrosis factor and interleukin-1 have decreased antithrombotic or prothrombotic properties and express leukocyte adhesion molecules to a greater extent. Cytokines, chemokines, and colony stimulating factors modulate the recruitment and activation of leukocytes. Activated platelets aggregate and bind to endothelial cells and to immobilized leukocytes, thus causing vascular occlusion accompanied by coagulation and leading to thrombosis. Cytokine activation may be limited by natural inhibitors or by therapeutic agents such as monoclonal antibodies, recombinant proteins, and drugs that alter cytokine synthesis, which may be of benefit in infection, inflammation, and possibly atherosclerosis.
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PMID:Cytokines and thrombosis. 869 51

Adhesion molecules have been demonstrated immunohistochemically on smooth muscle cells in atherosclerotic plaques. In endothelial cells cytokines are potent modulators of adhesion molecule expression. We therefore investigated the effects of cytokines on adhesion molecule expression on cultured human coronary and pulmonary smooth muscle cells by cell ELISA and confocal microscopy. Human coronary and pulmonary smooth muscle cells expressed ICAM-1 and VCAM-1 but not E-selectin. ICAM-1 expression was upregulated by TNF alpha, Il-1 beta and IFN-gamma. VCAM-1 expression was increased by TNF alpha and weakly by Il-1 beta, IFN-gamma had no effect on VCAM-1 expression. Cytokine effects on ICAM-1 and VCAM-1 were based on de novo synthesis. These results demonstrate that cytokines regulate ICAM-1 and VCAM-1 expression on human coronary and pulmonary smooth muscle cells. These effects may play an important role in the immune mechanisms in atherosclerosis.
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PMID:Modulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 on human coronary smooth muscle cells by cytokines. 882 78


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