UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Laminar shear stress (LSS) represents a major athero-protective stimulus. However, the mechanisms for this effect are poorly characterized. As chemokine receptors modulate endothelial cell functions, we hypothesized that at least some LSS effects on endothelial cells (ECs) may be due to LSS-dependent changes in chemokine receptor expression and function. Exposure of Human umbilical vein endothelial cells (HUVECs) to 15 dynes/cm2/sec(-1) LSS strongly inhibited CXC chemokine receptor 4 (CXCR4) expression at the transcriptional level and impaired stromal-derived factor (SDF)-1/CXCL12-driven chemotaxis. On the contrary, low shear stress (SS; 4 dynes/cm2/sec(-1)) only marginally affected CXCR4 expression when compared with static control cells. Differently from CXCR4, the expression of SDF-1 mRNA was not affected by LSS treatment. CXCR4 overexpression induced a dose-dependent endothelial cell apoptosis that was enhanced by SDF-1 treatment and was caspase-dependent. CXCR4 overexpression inhibited the LSS-mediated antiapoptotic effect on ECs and was associated to impairment of LSS-induced ERK1/2 phosphorylation. These findings suggest that LSS-induced CXCR4 down-regulation may contribute to endothelial cell survival. Interestingly, the expression of the proatherogenic chemokines MCP-1 and IL-8 was induced by SDF-1 treatment and by CXCR4 overexpression in HUVECs. Further, the known LSS-induced inhibition of MCP-1 expression was impaired in CXCR4 overexpressing ECs. Finally, CXCR4 was abundantly expressed by human atherosclerotic plaque endothelium that is exposed to low/absent shear stress, while it was poorly expressed by minimally diseased carotid artery endothelium. In conclusion, LSS-dependent CXCR4 down-regulation may contribute to atheroprotection by favoring the integrity of the endothelial barrier and by inhibiting MCP-1 and IL-8 expression.
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PMID:Laminar shear stress inhibits CXCR4 expression on endothelial cells: functional consequences for atherogenesis. 1570 41

TL1A (VEGI/TNFSF15) is the ligand for DR3 (TNFRSF12) and is a newly identified member of the tumor necrosis factor superfamily (TNFSF). Previously, DR3 has been shown to have a role in atherogenesis through stimulation of matrix degrading enzymes including matrix metalloproteinase (MMP)-9. Immunohistochemical staining of human carotid atherosclerotic plaques revealed a high-level expression of TL1A in regions rich in macrophage/foam cells. To investigate the role of TL1A and DR3 in the functioning of macrophage/foam cells in relation to atherogenesis, we have analyzed cellular events mediated by TL1A and DR3 in a human macrophage-like cell line, THP-1. Treatment of THP-1 cells with immobilized anti-DR3 monoclonal antibody in combination with IFN-gamma caused induction of pro-atherogenic cytokines/chemokines such as TNF-alpha, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-8. Treatment of THP-1 cells with recombinant TL1A in combination with IFN-gamma also caused induction of MMP-9 and IL-8. Furthermore, the expression of DR3 in peripheral blood monocytes was induced after atherogenic stimulation. These data suggest that TL1A and DR3 is involved in atherosclerosis via the induction of pro-inflammatory cytokines/chemokines and decreasing plaque stability by inducing extracellular matrix degrading enzymes.
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PMID:Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis. 1576 Jun 79

Our previous study demonstrated that homocysteine (Hcy) mediated the expression and secretion of MCP-1 and IL-8 in human monocytes. In the present study, we investigated whether the responsiveness of isolated monocytes to lipopolysaccharide (LPS)-induced chemokine secretion was enhanced in patients with hyperhomocysteinemia (HHcy), and if so, whether this enhanced response could be inhibited by folic acid treatment. We studied 38 control subjects and 40 patients with HHcy. The results showed that MCP-1 secretion from isolated monocytes in response to low-dose LPS in patients with HHcy was significantly higher than that in controls. After patients with HHcy underwent low-dose folic acid treatment (0.8 mg/d) for 6 months, plasma Hcy levels were decreased and the hyper-responsiveness of MCP-1 and IL-8 secreted by isolated monocytes was significantly reversed. Furthermore, folic acid treatment at high concentrations (5 microM) significantly reduced the elevated levels of reactive oxygen species, NADPH oxidase activity and chemokines in response to Hcy in cultured human monocytes. HHcy may contribute to atherogenesis through enhancing the responsiveness of monocytes to inflammatory stimuli and promoting leukocyte recruitment into atherosclerotic plaque. In addition to lowering the plasma levels of Hcy, low-dose folic acid treatment exerts beneficial effects on patients with HHcy by inhibiting pro-inflammatory responses such as chemokine secretion from human monocytes.
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PMID:Folic acid reverses hyper-responsiveness of LPS-induced chemokine secretion from monocytes in patients with hyperhomocysteinemia. 1577 59

Interleukin-8 is CXC chemokine that is initially discovered using chemotaxis and the activation of neutrophils and induces the migration and proliferation of smooth muscle cells. Interleukin-8 is a potent angiogenic factor that may play a role in atherosclerosis. To establish the temporal correlation between IL-8 expression and plaque development, we examined the expression during atherosclerosis of hyperlipemia rabbits using immunohistochemistry, ELISA, in situ hybridization. By location of immunohistochemistry, the expression of IL-8 protein increased obviously in intima of hyperlipemia rabbits at 8 and 12 week. Quantitative analysis of the expression of IL-8 Immunohistochemistry indicated that positive area of AS model was 4.48 times and 8.76 times that of control group at 8 and 12 week. The valuation of IOD of AS model was 4.16 times and 4.36 times that of control group at 8 and 12 week. By specific ELISA, the ratio of the IL-8 protein to total protein of AS model was 1.84 times and 2.06 times that of control group at 8 and 12 week. By location of in situ hybridization, positive location was strong in intima of hyperlipemia rabbits at 8 week. We observed the dynamic alteration of interleukin-8 protein and gene expression in atherosclerotic lesions of hyperlipemia rabbits with establishing model. Interleukin-8 protein and gene expression was up-regulation in the development of fatty streaks in hyperlipemia rabbit.
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PMID:[Interleukin-8 protein and gene expression in atherosclerotic lesions of hyperlipemia rabbits]. 1588 31

Narrow-band ultraviolet B (UVB) phototherapy is an effective treatment for psoriasis. Owing to its limited penetration, the direct effects of UVB are mostly restricted to cells residing in the epidermis and papillary dermis, and are associated with epidermal depletion of Langerhans' cells (LC) and T cells. It has been argued that the depletion of the skin-resident T-cell population may be due to a combination of UVB-induced apoptosis and decreased recruitment from the blood due to lower expression of the required adhesion and homing molecules. We have previously demonstrated that UVB treatment can alter the expression of adhesion molecules by blood lymphocytes, and as these can be influenced by cytokines, the aim of this study was to investigate whether UVB irradiation can also influence the cytokine production of circulating T cells. Four patients with active chronic plaque psoriasis were treated daily with narrow-band 312 nm UVB irradiation and blood samples obtained before treatment and weekly thereafter for 2 weeks. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured with a streptococcal superantigen or a conventional streptococcal antigen preparation, and cell culture supernatants were assayed for various cytokines. When stimulated with the superantigen, PBMCs from UVB-treated psoriasis patients secreted greater amounts of the anti-inflammatory cytokine IL-10, and showed markedly decreased production of IL-1beta, IL-2, IL-5 and IL-6 compared to the pre-treatment values; the production of IFN-gamma, IL-8 and IL-12p70 were also decreased but did not reach statistical significance. Thus, the combination of UVB-induced apoptosis, increased secretion of anti-inflammatory cytokines and decreased trafficking to the skin may help to explain the beneficial effects of UVB treatment on psoriasis and why disease remission can sometimes be sustained for a prolonged period.
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PMID:Narrowband-UVB irradiation decreases the production of pro-inflammatory cytokines by stimulated T cells. 1588 64

The pathogenesis of skin scleroderma (LS) is still unknown. Disturbances of vessels system, connective tissue metabolism and humoral and cellular immunological response is observed. Antinuclear antibodies are detected in 30-80% of patients with different types of skin scleroderma. They are present more often in patients with disseminated lesions and linear type of LS compared to morphoea au plaque. In our own analysis 28.5% of patients had also antibodies directed against Borrelia burgdorferi. It is believed that the injury of endothelial cells and proliferation in medial part of small vessels - which both lead to chronic ischemia - are the earliest disturbances observed in histopathological examination of the skin taken from systemic as well as from skin scleroderma patients. During last few years, there were some interesting reports concerning functional changes of endothelial cells which led to disturbances in tension of vessels smooth muscles. Free radicals - in genetically predispose people--can also provoke scleroderma lesions through their injury action on endothelial cells and stimulation of fibroblasts. In morphoea, the process of fibrosis begins around vessels. Deposition of connective tissue matrix is observed, especially collagen type I and III. This stimulation of fibroblasts as well as accumulation of connective tissue matrix are secondary to some stimulatory factors. These are: PDF, bFGF, TGFbeta and some cytokines. In morphoea patients serum levels of IL-1, IL-2, IL-4, IL-6 and IL-8 were elevated. In literature, levels and production of collagenases were decreased, although more authors say that tissue inhibitors of metalloproteinases are the main factor in fibrosis. The analysis of data tends to suspicion that enormous fibrosis observed in different types of scleroderma can be the result of increased production of collagen and other components of connective tissue as well as their incomplete degradation. Presented clinical and laboratory data show how many different factors influence etiopathogenesis of morphoea.
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PMID:[Pathogenesis of skin scleroderma--literature review]. 1633 38

Helicobacter pylori (H. pylori) is an important gastrointestinal pathogen associated with gastritis as well as gastric or duodenal ulcers and gastric cancer. The oral cavity has been considered as a potential reservoir for the gastric infection and reinfection. The objective of our studies was to evaluate the influence of oral H. pylori for the stomach infection and the release of gut hormones affecting food intake such as ghrelin and gastric secretion such as gastrin. Additionally, the contribution of H. pylori in the periodontal disease has been examined. H. pylori infection in stomach was assessed by (13)C- Urease Breath Test and presence of the bacteria in oral cavity by culture. The periodontal status was measured by pockets depth with the periodontal probe. We estimated the serum level of IgG anti-H. pylori, anti-VacA, anti-CagA, ghrelin, gastrin, TNF-alpha and IL-8 in blood and the level of IgA anti-H. pylori in saliva. The presence of H. pylori in oral cavity was detected in 54.1% of examined individuals, whereas the H. pylori gastric infection in tested group was found in 51% cases. However, the correlation analysis between those two groups of patients involving together about 100 subjects showed that within the group of patients with positive gastric H. pylori infection only 45.1% did not show the presence of H. pylori in saliva and 43.1% showed no H. pylori in supragingival plaque. In line of these findings patients who did not have gastric H. pylori infection, 53.2% showed presence of H. pylori in saliva and 42.9% in supragingival plaques. Serum level of ghrelin and gastrin in subjects with oral H. pylori inoculation but without gastric H. pylori infection were not significantly different from those without the presence of this germ in oral cavity. In contrast, gastric H. pylori infection resulted in significant reduction in serum ghrelin levels and significant elevation of gastrin as compared to those who were gastric H. pylori negative. We concluded that oral H. pylori alone does not seem to serve as bacterium sanctuary for gastric H. pylori infection and, unlike gastric infection, it fails to affect serum levels of hormones stimulating appetitive behaviour such as ghrelin and gastric acid secretion such as gastrin.
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PMID:Helicobacter pylori in the oral cavity and its implications for gastric infection, periodontal health, immunology and dyspepsia. 1634 41

Epidemiological studies support that chronic periodontal infections are associated with an increased risk of cardiovascular disease. Previously, we reported that the periodontal pathogen Porphyromonas gingivalis accelerated atherosclerotic plaque formation in hyperlipidemic apoE-/- mice, while an isogenic fimbria-deficient (FimA-) mutant did not. In this study, we utilized 41 kDa (major) and 67 kDa (minor) fimbria mutants to demonstrate that major fimbria are required for efficient P. gingivalis invasion of human aortic endothelial cells (HAEC). Enzyme-linked immunosorbent assay (ELISA) revealed that only invasive P. gingivalis strains induced HAEC production of pro-inflammatory molecules interleukin (IL)-1beta, IL-8, monocyte chemoattractant protein (MCP)-1, intracellular adhesion molecule (ICAM)-1, vascular cellular adhesion molecule (VCAM)-1 and E-selectin. The purified native forms of major and minor fimbria induced chemokine and adhesion molecule expression similar to invasive P. gingivalis, but failed to elicit IL-1beta production. In addition, the major and minor fimbria-mediated production of MCP-1 and IL-8 was inhibited in a dose-dependent manner by P. gingivalis lipopolysaccharide (LPS). Both P. gingivalis LPS and heat-killed organisms failed to stimulate HAEC. Treatment of endothelial cells with cytochalasin D abolished the observed pro-inflammatory MCP-1 and IL-8 response to invasive P. gingivalis and both purified fimbria, but did not affect P. gingivalis induction of IL-1beta. These results suggest that major and minor fimbria elicit chemokine production in HAEC through actin cytoskeletal rearrangements; however, induction of IL-1beta appears to occur via a separate mechanism. Collectively, these data support that invasive P. gingivalis and fimbria stimulate endothelial cell activation, a necessary initial event in the development of atherogenesis.
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PMID:Fimbria-dependent activation of pro-inflammatory molecules in Porphyromonas gingivalis infected human aortic endothelial cells. 1661 Dec 24

Accumulating evidence support a role of neutrophils in coronary artery disease (CAD). However little is known about the action of neutrophils at a local inflammatory site represented by an atherosclerotic plaque. To gain insight into these issues, we applied a skin blister model that permits analyses of in vivo transmigrated neutrophils. We hypothesised that the chronic inflammation in stable CAD mediates priming of neutrophils that impacts the out-come of neutrophil action at an inflammatory site. Thirteen patients with angiographically verified CAD were eligible for study entry together with 13 age and sex matched controls. Markers of inflammation (IL-6 and CRP), neutrophil activation (IL-8 and MMP-9/NGAL), and functional aspects (CD11b up-regulation and intracellular H(2)O(2) production) of peripheral and in vivo transmigrated neutrophils were studied. Systemic IL-8 and MMP-9/NGAL concentrations were significantly increased in patients indicating a primed state in circulating neutrophils. In vivo transmigrated neutrophils in stable CAD patients had an increased propensity to release MMP-9/NGAL and a reduced capacity to up-regulate CD11b and to produce hydrogen peroxide. These aberrations at the inflammatory site may be a consequence of a primed state of circulating neutrophils and point towards potential mechanisms whereby neutrophils at a local inflammatory site may contribute to the pathogenesis of CAD.
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PMID:Activation of peripheral and in vivo transmigrated neutrophils in patients with stable coronary artery disease. 1696 51

Humans develop periodontitis in response to challenge by microbial dental plaque. Inflammation begins after perturbation of gingival epithelial cells by subgingival bacteria interacting through pattern-recognition receptors, including the Toll-like receptors (TLR). Porphyromonas gingivalis is a major periodontopathogen that interacts with epithelial cells through its cell surface fimbriae (FimA), leading to colonization and/or invasion. Previous work by our group has established membrane CD14 as an essential coreceptor for TLR2-mediated activation of transfected cell lines by P. gingivalis FimA. We have shown that gingival epithelial cells express TLR2 but not CD14 on their cell surfaces. We thus speculated that P. gingivalis FimA does not readily activate epithelial innate immune responses but rather functions to promote P. gingivalis colonization in the absence of a vigorous FimA-induced response. This hypothesis was verified by the findings that primary human gingival epithelial cells responded poorly to FimA in terms of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha responses, in stark contrast to the marked response to other TLR2 agonists (Pam3Cys, FSL-1) that are not strictly dependent on CD14. On the other hand, CD14-expressing human primary monocytes responded with high levels of the same cytokines to both FimA and the control TLR2 agonists. The gingival epithelial cells failed to respond to FimA even in the presence of exogenously added soluble CD14. These data indicate that the gingival epithelial cell hyporesponsiveness to FimA is attributable to the lack of membrane-expressed but not soluble CD14. In conclusion, P. gingivalis FimA differentially activates human monocytes and epithelial cells, perhaps reflecting different tactics used by P. gingivalis when interacting with different host cell types or a host strategy to limit inflammation.
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PMID:Differential activation of human gingival epithelial cells and monocytes by Porphyromonas gingivalis fimbriae. 1711 77

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