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)

As a kind of chemokine, IL-8 plays an important role in inflammatory reaction. Its expression in endothelial cells is regulated by a variety of cytokines. In this study, after incubating cultured human umbilical vein endothelial cells(HUVECs) with TNF-alpha for different time, we employed RT-PCR to assay IL-8 mRNA expression and immunocytochemical staining to detect NF-kappa B activation in HUVECs. The results revealed: (1) IL-8 mRNA expressed little in untreated HUVECs; after HUVECs was pre-incubated with TNF-alpha for 1 hour, IL-8 mRNA expression increased greatly, and it increased further after pre-incubated for 3 hours; however, when HUVECs was pre-incubated with TNF-alpha for 6 hours, IL-8 mRNA expression decreased, and it almost decreased to basal level when pre-incubated for 9 hours; (2) the immunoreactivity of NF-kappa B p65 in the nuclei of untreated HUVECs was negative; it became positive in the nuclei of HUVECs pre-incubated with TNF-alpha for 1 hour and 3 hours; it became weak positive in the nuclei of HUVECs pre-incubated with TNF-alpha for 6 hours, and after 9 hours, pre-incubation, the immunoreactivity of NF-kappa B p65 in the nuclei of HUVECs was negative. These results implied that TNF-alpha was capable of inducing IL-8 gene expression and activation NF-kappa B. and Their time courses were similar, thus suggesting that the induction of IL-8 gene expression by TNF-alpha is probably due to the activation of NF-kappa B.
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PMID:[Effects of TNF-alpha on IL-8 mRNA expression in endothelial cells]. 1133 87

This study sought to demonstrate that IL-8 expression in endothelial cells is regulated by not only chemical factors but also mechanical factors. After pretreating cultured human umbilical vein endothelial cells (HUVECs) with shear stress for different periods of time, we employed RT-PCR to assay IL-8 mRNA expression and immunocytochemical staining to detect NF-kappa B activation in HUVECs. The results showed: 1. IL-8 mRNA expressed little in HUVECs untreated or pretreated with low laiminar shear stress for 0.5 h; IL-8 mRNA expression increased when HUVECs were pretreated with low laminar shear stress for 1 h, and it increased further when HUVECs were pretreated for 2 h; 2. The immunoreactivity of NF-kappa B p65 in the nuclei of HUVECs untreated or pretreated with low laminar shear stress for 0.5 h was negative, while it became weak positive in the nuclei of HUVECs pretreated with shear stress for 1 h and positive in the nuclei of HUVECs pretreated for 2 h. The findings implied that low laminar shear stress was capable of inducing IL-8 gene expression and activating NF-kappa B, which were both time-dependent. The induction of IL-8 gene expression by laminar shear stress is probably due to the activation of NF-kappa B. On these grounds we come to the conclusion that IL-8 expression induced in endothelial cells by low shear stress may play an important role in the genesis and development of both inflammation and arterioatherosclerosis.
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PMID:[Effects of laminar shear stress on IL-8 mRNA expression in endothelial cells]. 1133 18

Activated hepatic stellate cells (HSCs) are the main producers of extracellular matrix in the fibrotic liver and contribute to hepatic inflammation through the secretion of chemokines and the recruitment of leukocytes. This study assesses the function of CD40 on human HSCS: Activated human HSCs express CD40 in culture and in fibrotic liver, as determined by flow cytometry, RT-PCR, and immunohistochemistry. CD40 expression is strongly enhanced by IFN-gamma. Stimulation of CD40 with CD40 ligand (CD40L)-transfected baby hamster kidney cells induces NF-kappaB, as demonstrated by the activation of I-kappaB kinase (IKK), increased NF-kappaB DNA binding, and p65 nuclear translocation. CD40-activated IKK also phosphorylates a GST-p65 substrate at serine 536 in the transactivation domain 1. Concomitant with the activation of IKK, CD40L-transfected baby hamster kidney cell treatment strongly activates c-Jun N-terminal kinase. CD40 activation increases the secretion of IL-8 and monocyte chemoattractant protein-1 by HSCs 10- and 2-fold, respectively. Adenovirally delivered dominant negative (dn) IKK2 and TNFR-associated factor 2dn inhibit IKK-mediated GST-I-kappaB and GST-p65 phosphorylation, NF-kappaB binding, and IL-8 secretion, whereas IKK1dn and NF-kappaB-inducing kinase dominant negative do not have inhibitory effects. We conclude that the CD40-CD40L receptor-ligand pair is involved in a cross-talk between HSCs and immune effector cells that contributes to the perpetuation of HSC activation in liver fibrosis through TNFR-associated factor 2- and IKK2-dependent pathways.
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PMID:CD40 activates NF-kappa B and c-Jun N-terminal kinase and enhances chemokine secretion on activated human hepatic stellate cells. 1135 40

Sin Nombre virus (SNV) and Hantaan virus (HTN) infect endothelial cells and are associated with different patterns of increased vascular permeability during human disease. It is thought that such patterns of increased vascular permeability are a consequence of endothelial activation and subsequent dysfunction mediated by differential immune responses to hantavirus infection. In this study, the ability of hantavirus to directly induce activation of human lung microvascular endothelial cells (HMVEC-Ls) was examined. No virus-specific modulation in the constitutive or cytokine-induced expression of cellular adhesion molecules (CD40, CD54, CD61, CD62E, CD62P, CD106, and major histocompatibility complex classes I and II) or in cytokines and chemokines (eotaxin, tumor necrosis factor alpha, interleukin 1beta [IL-1beta], IL-6, IL-8, MCP-1, MIP-1alpha, and MIP-1beta) was detected at either the protein or message level in hantavirus-infected HMVEC-Ls. Furthermore, no virus-specific enhancement of paracellular or transcellular permeability or changes in the organization and distribution of endothelial intercellular junctional proteins was observed. However, infection with either HTN or SNV resulted in detectable levels of the chemokines RANTES and IP-10 (the 10-kDa interferon-inducible protein) in HMVEC-Ls within 72 h and was associated with nuclear translocation of interferon regulatory factor 3 (IRF-3) and IRF-7. Gamma interferon (IFN-gamma)-induced expression of RANTES and IP-10 could also be detected in uninfected HMVEC-Ls and was associated with nuclear translocation of IRF-1 and IRF-3. Treatment of hantavirus-infected HMVEC-Ls with IFN-gamma for 24 h resulted in a synergistic enhancement in the expression of both RANTES and IP-10 and was associated with nuclear translocation of IRF-1, IRF-3, IRF-7, and NF-kappaB p65. These results reveal a possible mechanism by which hantavirus infection and a TH1 immune response can cooperate to synergistically enhance chemokine expression by HMVEC-Ls and trigger immune-mediated increases in vascular permeability.
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PMID:Hantavirus infection induces the expression of RANTES and IP-10 without causing increased permeability in human lung microvascular endothelial cells. 1139 Jun 9

Hyperhomocysteinemia is an independent risk factor for atherosclerosis and atherothrombosis. While in vitro studies have revealed a number of homocysteine-mediated alterations in the thromboregulatory properties of endothelial cells, comparatively little is known about homocysteine-modulated smooth muscle cell function. We observed that exposure of human aortic smooth muscle cells to pathophysiologically relevant concentrations of homocysteine results in concentration-dependent increases in cytokine-induced MCP-1 and IL-8 secretion. RNase protection assays revealed that both MCP-1 and IL-8 mRNA concentrations are increased in homocysteine-treated smooth muscle cells when compared to cells activated with cytokines alone. Homocysteine treatment also increased cytosolic-to-nuclear translocation of the p65 and p50 subunits of the Rel/NF-kappaB family of transcription factors but had no effect on AP-1 activation. Cumulatively, these data suggest that homocysteine may increase monocyte recruitment into developing atherosclerotic lesions by upregulating MCP-1 and IL-8 expression in vascular smooth muscle cells.
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PMID:Homocysteine augments cytokine-induced chemokine expression in human vascular smooth muscle cells: implications for atherogenesis. 1140 9

Constitutive IKK activity associated with increased IkappaBalpha phosphorylation and degradation contribute to the high level of endogenous nuclear factor-kappaB (NF-kappaB) activation in Hs294T melanoma cells as compared with RPE cells (R. L. Shattuck-Brandt and A. Richmond, Cancer Res., 57: 3032-3039, 1997; M. N. Devalaraja et al., Cancer Res., 59: 1372-1377, 1999). To determine whether this endogenous NF-kappaB activation was characteristic of melanoma, we examined the level of constitutive activation of NF-kappaB in a number of melanoma cell lines. We demonstrate here that eight melanoma cell lines exhibit increased IkappaB kinase (IKK) activity, enhanced phosphorylation of IkappaBalpha and p65, and enhanced nuclear localization of p65/p50 in comparison to normal human epidermal melanocytes. The chemokines, CXC ligand 1 (CXCL1) and CXCL8, but not CXCL5, are highly expressed in most of the melanoma cell lines, suggesting that the constitutive production of chemokines is highly correlated to endogenous NF-kappaB activity. Our failure to observe a direct relationship between the fold activation of IKK, CXCL1, or CXCL8 mRNA levels and secretion of these chemokines into the culture medium suggest that regulation of chemokine expression also occurs at the posttranscription level of mRNA stability and/or translational control. Moreover, recombinant CXCL1 can directly induce IKK activity in normal human epidermal melanocytes in a concentration-dependent manner after up-modulation of CXCL1 protein expression, whereas inhibition of IKKbeta activity results in down-modulation of CXCL1 protein expression. Finally, CXCL1 antibody blocks IKK activity and inhibits the proliferation of melanoma cells to further support the concept that the constitutive activation of NF-kappaB and autocrine effects of CXCL1 play an important role in the pathogenesis of melanoma.
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PMID:Constitutive IkappaB kinase activity correlates with nuclear factor-kappaB activation in human melanoma cells. 1140 69

Geldanamycin is a benzoquinone ansamycin with multiple pharmacologic properties. Recent data demonstrated that geldanamycin conferred protection in an animal model of inflammation-associated acute lung injury. In the current study, we investigated the effects of geldanamycin on interleukin (IL)-8 gene expression and nuclear factor (NF)-kappaB activation. Geldanamycin inhibited tumor necrosis factor (TNF)-alpha-mediated IL-8 gene expression in A549 human respiratory epithelial cells as measured by enzyme-linked immunosorbent assay and Northern blot analyses. In cells transiently transfected with an IL-8 promoter-luciferase reporter plasmid, geldanamycin inhibited TNF-alpha-mediated luciferase activity. Geldanamycin inhibited TNF-alpha-mediated NF-kappaB activation as measured by electromobility shift assays and transient transfections with a NF-kappaB-dependent luciferase reporter plasmid. In contrast, geldanamycin did not affect TNF-alpha-mediated degradation of the NF-kappaB inhibitory protein IkappaBalpha and did not block nuclear translocation of the NF-kappaB p65 subunit as measured by Western blot analyses. Geldanamycin added directly to nuclear extracts of TNF-alpha-treated cells reduced the formation of the NF-kappaB/DNA complex. These results demonstrate that geldanamycin inhibits TNF-alpha-mediated IL-8 gene expression in A549 cells by inhibiting activation of the IL-8 promoter. The mechanism of inhibition involves inhibition of NF-kappaB activation, which is independent of IkappaBalpha degradation or p65 nuclear translocation. Geldanamycin appears to directly inhibit the ability of NF-kappaB to bind DNA. The observed in vitro effects could account, in part, for the anti-inflammatory properties of geldanamycin observed in vivo.
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PMID:Geldanamycin inhibits NF-kappaB activation and interleukin-8 gene expression in cultured human respiratory epithelium. 1147 80

Increasing evidence indicates that intracellular redox status modulates the activity of various transcriptional factors, including nuclear factor (NF)-kappa B and activator protein-1. Our laboratory has been interested in characterizing the role thioredoxin (TRX) plays in regulating cellular redox status in airway epithelium. TRX is a small, ubiquitous protein with two redox-active half-cysteine residues, -Cys-Gly-Pro-Cys, in its active center. Using primary passage-1 human tracheobronchial epithelial cell cultures and an immortalized human bronchial epithelial cell line, HBE1, we observed that tumor necrosis factor (TNF)-alpha enhanced NF-kappa B transcriptional activity. This observation was based on gel mobility shift assays and interleukin (IL)-8 promoter-reporter gene transfection studies. TNF-alpha activation coincided with translocation of NF-kappa B p65 from the cytoplasm to the nucleus. Pretreatment with N-acetyl-cysteine (NAC) (1 to 10 mM) or glutathione (1 to 10 mM) inhibited TNF-alpha-induced activation of NF-kappa B transcriptional activity and IL-8 promoter-mediated reporter gene expression. In contrast, elevated TRX protein levels in cells enhanced TNF-alpha-dependent NF-kappa B transcriptional activity and IL-8 promoter activity. This observation was independent of the manner in which TRX was elevated in cells (e.g., by cotransfection with a FLAG-TRX expression clone, or by direct exposure to commercially available human TRX protein). Localization of TRX protein by anti-TRX antibody indicated an accumulation of TRX protein in the nucleus after TNF-alpha treatment. The nuclear localization phenomenon was different from the major cytosolic accumulation of glutathione and NAC. This is the first known report demonstrating movement of TRX into the nucleus of airway epithelial cells after an inflammatory stress. These results suggest a compartment effect of thiol chemicals in the regulation of redox-dependent transcriptional activity.
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PMID:Activation of nuclear factor-kappa b transcriptional activity in airway epithelial cells by thioredoxin but not by N-acetyl-cysteine and glutathione. 1150 27

African swine fever (ASF) is an asymptomatic infection of warthogs and bushpigs, which has become an emergent disease of domestic pigs, characterized by hemorrhage, lymphopenia, and disseminated intravascular coagulation. It is caused by a large icosohedral double-stranded DNA virus, African swine fever virus (ASFV), with infection of macrophages well characterized in vitro and in vivo. This study shows that virulent isolates of ASFV also infect primary cultures of porcine aortic endothelial cells and bushpig endothelial cells (BPECs) in vitro. Kinetics of early and late gene expression, viral factory formation, replication, and secretion were similar in endothelial cells and macrophages. However, ASFV-infected endothelial cells died by apoptosis, detected morphologically by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and nuclear condensation and biochemically by poly(ADP-ribose) polymerase (PARP) cleavage at 4 h postinfection (hpi). Immediate-early proinflammatory responses were inhibited, characterized by a lack of E-selectin surface expression and interleukin 6 (IL-6) and IL-8 mRNA synthesis. Moreover, ASFV actively downregulated interferon-induced major histocompatibility complex class I surface expression, a strategy by which viruses evade the immune system. Significantly, Western blot analysis showed that the 65-kDa subunit of the transcription factor NF-kappaB, a central regulator of the early response to viral infection, decreased by 8 hpi and disappeared by 18 hpi. Both disappearance of NF-kappaB p65 and cleavage of PARP were reversed by the caspase inhibitor z-VAD-fmk. Interestingly, surface expression and mRNA transcription of tissue factor, an important initiator of the coagulation cascade, increased 4 h after ASFV infection. These data suggest a central role for vascular endothelial cells in the hemorrhagic pathogenesis of the disease. Since BPECs infected with ASFV also undergo apoptosis, resistance of the natural host must involve complex pathological factors other than viral tropism.
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PMID:African swine fever virus infection of porcine aortic endothelial cells leads to inhibition of inflammatory responses, activation of the thrombotic state, and apoptosis. 1158 5

Interleukin-18 (IL-18) is a novel proinflammatory cytokine that was recently found in synovial fluids and in synovial tissues from patients with rheumatoid arthritis (RA). To determine the participation of IL-18 in the inflammation observed in RA, we investigated the effect of IL-18 on RA synovial fibroblast chemokine production. Using FACS analysis, we showed that IL-18 induced a doubling in the production of intracellular IL-8 by RA synovial fibroblasts, and this result was confirmed by Western blot. At the extracellular level, IL-18 up-regulated the secretion of IL-8 in a dose- and time-dependent manner. IL-18 also up-regulated the other CXC chemokines, epithelial-neutrophil activating protein (ENA-78) and growth-regulated oncogene (groalpha), in a dose dependent manner, but failed to induce the production of the CC chemokine, macrophage inflammatory protein (MIP)-1alpha. By immunofluorescence and Western blot, we demonstrated that IL-18 activates the translocation of the transcription factor nuclear factor kappa B (NFkappaB) into the nucleus of RA synovial fibroblasts. IL-18 induces IL-8 secretion through NFkappaB because RA synovial fibroblasts pretreated with antisense to NFkappaB p65 oligonucleotide produce a mean of 44% less IL-8 compared with cells pretreated with the control sense oligonucleotide. These results indicate a novel role for IL-18 in inducing RA synovial fibroblast expression of CXC chemokines through NFkappaB and place this cytokine in a strategic role in the local inflammation observed in RA.
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PMID:Interleukin-18 induces rheumatoid arthritis synovial fibroblast CXC chemokine production through NFkappaB activation. 1159 50

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