Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An important role for selenium in human immunodeficiency virus (HIV) disease has been proposed. Decreased selenium levels, as found in persons with HIV infection or AIDS, are sensitive markers of disease progression. Selenium deficiency, an independent predictor of mortality in both HIV-1-infected adults and children, is an essential micronutrient that is associated with an improvement of T cell function and reduced apoptosis in animal models. In addition, adequate selenium may enhance resistance to infections through modulation of interleukin (IL) production and subsequently the Th1/Th2 response. Selenium supplementation up-regulates IL-2 and increases activation, proliferation, differentiation, and programmed cell death of T helper cells. Moreover, selenium supplementation may down-regulate the abnormally high levels of IL-8 and tumor necrosis factor-alpha observed in HIV disease, which has been associated with neurologic damage, Kaposi's sarcoma, wasting syndrome, and increased viral replication. Together, these findings suggest a new mechanism through which selenium may affect HIV-1 disease progression.
 ...
PMID:Selenium and interleukins in persons infected with human immunodeficiency virus type 1. 1094 86

Human CMV (HCMV) retinitis frequently leads to blindness in iatrogenically immunosuppressed patients and in the end stage of AIDS. Despite the general proinflammatory potential of HCMV, virus infection is associated with a rather mild cellular inflammatory response in the retina. To investigate this phenomenon, the influence of HCMV (strains AD169 or Hi91) infection on C-X-C chemokine secretion, ICAM-1 expression, and neutrophil recruitment in cultured human retinal pigment epithelial (RPE) cells was studied. Supernatants from infected cultures contained enhanced levels of IL-8 and melanoma growth-stimulating activity/Gro alpha and induced neutrophil chemotaxis compared with supernatants from uninfected RPE cells. Despite HCMV-induced ICAM-1 expression on RPE cells, binding of activated neutrophils to HCMV-infected RPE cells and subsequent transepithelial penetration were significantly reduced. Reduced neutrophil adhesion to infected RPE cells correlated with HCMV-induced up-regulation of constitutive Fas ligand (FasL) expression. Functional blocking of FasL on RPE cells with the neutralizing mAbs NOK-1 and NOK-2 or of the Fas receptor on neutrophils with mAbB-D29 prevented the HCMV-induced impairment of neutrophil/RPE interactions. Fas-FasL-dependent impairment of neutrophil binding had occurred by 10 min after neutrophil/RPE coculture without apoptotic signs. Neutrophil apoptosis was first detected after 4 h. Treatment of neutrophils with a specific inhibitor of caspase-8 suppressed apoptosis, whereas it did not prevent impaired neutrophil binding to infected RPE. The current results suggest a novel role for FasL in the RPE regulation of neutrophil binding. This may be an important feature of virus escape mechanisms and for sustaining the immune-privileged character of the retina during HCMV ocular infection.
 ...
PMID:Decreased neutrophil adhesion to human cytomegalovirus-infected retinal pigment epithelial cells is mediated by virus-induced up-regulation of Fas ligand independent of neutrophil apoptosis. 1103 78

IL10 is a powerful TH-2 cell cytokine produced by lymphoid cells that limits HIV-1 replication in vivo, ostensibly by inhibiting macrophage/monocyte and T-cell lymphocyte replication and secretion of inflammatory cytokines (IL1, TNFalpha, IL6, IL8, and IL12). A genetic epidemiological scan of patients enrolled in AIDS cohorts for candidate gene-linked short tandem repeat polymorphisms revealed significant genotype associations for HIV-1 infection and progression to AIDS with markers adjacent to and tracking (by linkage disequilibrium) common single nucleotide polymorphic variants in the IL10 promoter region. Individuals carrying the IL10-5'-592A (IL10-5'A) promoter allele possibly were at increased risk for HIV-1 infection, and once infected they progressed to AIDS more rapidly than homozygotes for the alternative IL10-5'-592 C/C (IL10-+/+) genotype, particularly in the later stages of HIV-1 infection. An estimated 25-30% of long-term nonprogressors (who avoid clinical AIDS for 10 or more years after HIV-1 infection) can be attributed to their IL10-+/+ promoter genotype. Alternative IL10 promoter alleles are functionally distinct in relative IL10 production, in retention of an avian erythroblastosis virus transcription factor recognition sequence and in binding to specific putative nuclear transcription factors, suggesting a potential mechanism whereby IL10-5'A down-regulation of inhibitory IL10 facilitates HIV-1 replication in vivo, accelerating the onset of AIDS.
 ...
PMID:Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10. 1112 Oct 48

Sambucus nigra L. products - Sambucol - are based on a standardized black elderberry extract. They are natural remedies with antiviral properties, especially against different strains of influenza virus. Sambucol was shown to be effective in vitro against 10 strains of influenza virus. In a double-blind, placebo-controlled, randomized study, Sambucol reduced the duration of flu symptoms to 3-4 days. Convalescent phase serum showed a higher antibody level to influenza virus in the Sambucol group, than in the control group. The present study aimed to assess the effect of Sambucol products on the healthy immune system - namely, its effect on cytokine production. The production of inflammatory cytokines was tested using blood - derived monocytes from 12 healthy human donors. Adherent monocytes were separated from PBL and incubated with different Sambucol preparations i.e., Sambucol Elderberry Extract, Sambucol Black Elderberry Syrup, Sambucol Immune System and Sambucol for Kids. Production of inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, IL-8) was significantly increased, mostly by the Sambucol Black Elderberry Extract (2-45 fold), as compared to LPS, a known monocyte activator (3.6-10.7 fold). The most striking increase was noted in TNF-alpha production (44.9 fold). We conclude from this study that, in addition to its antiviral properties, Sambucol Elderberry Extract and its formulations activate the healthy immune system by increasing inflammatory cytokine production. Sambucol might therefore be beneficial to the immune system activation and in the inflammatory process in healthy individuals or in patients with various diseases. Sambucol could also have an immunoprotective or immunostimulatory effect when administered to cancer or AIDS patients, in conjunction with chemotherapeutic or other treatments. In view of the increasing popularity of botanical supplements, such studies and investigations in vitro, in vivo and in clinical trials need to be developed.
 ...
PMID:The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. 1139 18

Kaposi's sarcoma-associated herpesvirus (KSHV) is believed to be the causative agent of Kaposi's sarcoma (KS), a multicentric growth factor-dependent tumor common in AIDS patients characterized histopathologically by spindle cell proliferation, angiogenesis, and leukocyte infiltration. Recently, open reading frame 74 of KSHV has been implicated as a major viral determinant of KS. Open reading frame 74 encodes KSHV G protein-coupled receptor (GPCR), a constitutively active chemokine receptor that directly transforms NIH 3T3 cells in vitro and induces multifocal KS-like lesions in KSHV-GPCR-transgenic mice. Interestingly, receptor-positive cells are very rare in lesions from these mice, implicating an indirect mechanism of tumorigenesis. In this regard, here we report that expression of KSHV-GPCR in transfected epithelial, monocytic, and T cell lines induced constitutive activation of the immunoregulatory transcription factors AP-1 and NF-kappaB. This was associated with constitutive induction of the proinflammatory NF-kappaB-dependent cytokines IL-1beta, IL-6, and TNF-alpha, and chemokines monocyte chemoattractant protein-1 and IL-8, as well as the AP-1-dependent basic fibroblast growth factor. In addition, IL-2 and IL-4 production was induced in transfected Jurkat T cells. Truncation of the final five amino acids in the cytoplasmic tail of KSHV-GPCR caused complete loss of its transforming and NF-kappaB-inducing activities, without affecting receptor expression or ligand binding. These data suggest that KS results in part from KSHV-GPCR induction of proinflammatory cytokine and growth factor gene expression, mediated by a signaling determinant within the last five amino acids of the C terminus, a domain that is also critical for direct cell transformation.
 ...
PMID:Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor constitutively activates NF-kappa B and induces proinflammatory cytokine and chemokine production via a C-terminal signaling determinant. 1141 89

C/EBPbeta is a member of a family of leucine zipper transcription factors that are involved in regulating the expression of several cytokines, including IL-1, IL-6, IL-8, TNF, and macrophage-inflammatory protein-1alpha. We identified multiple C/EBPbeta binding sites within the gene for CCR5, suggesting that C/EBPbeta may be involved in its regulation. Transient transfection experiments in both myeloid and lymphoid cells showed an increase in CCR5 promoter-driven green fluorescent protein production in the presence of C/EBPbeta. Deletion analysis identified two C/EBPbeta-responsive regions in the CCR5 gene, one in the promoter region and one at the 3' part of the intron. We provide evidence that, in myeloid cells (U937), C/EBPbeta independently activates CCR5 expression through sites located either in the promoter region or in the intron of the CCR5 gene. In contrast, in lymphoid cells (Jurkat) the presence of the intronic cis-regulatory regions is required for C/EBPbeta-mediated activation. In agreement with the functional data, EMSA demonstrated that in both myeloid and lymphoid cells C/EBPbeta binds specifically to sites present in the intron, whereas interaction with the sites located in the promoter was cell type specific and was detected only in myeloid cells. Analysis of C/EBPbeta in primary PBMCs obtained from HIV-1-infected individuals revealed a significant increase in C/EBPbeta expression. The enhanced C/EBPbeta activity correlated with a higher frequency of circulating CCR5(+) lymphocytes in AIDS patients and with a decline in CD4 lymphocyte numbers. Taken together, these results suggest that C/EBPbeta is an important regulator of CCR5 expression and may play a relevant role in the pathogenesis of HIV disease.
 ...
PMID:CCAAT-enhancer-binding protein beta (C/EBP beta) activates CCR5 promoter: increased C/EBP beta and CCR5 in T lymphocytes from HIV-1-infected individuals. 1146 89

Kaposi's sarcoma (KS) is the most common tumor associated with HIV-1 infection. Here, we report the expression, regulation, and biological effect of interleukin (IL)-8 in KS. AIDS-KS cell lines expressed higher levels of IL-8 than either human umbilical vein endothelial cells (HUVECs), human aortic smooth muscle (AoSM) cells or fibroblast cells (T1). The inflammatory cytokine IL-1beta up-regulated IL-8 expression in a time- and concentration-dependent manner in KS cell lines. IL-8 antisense oligonucleotides specifically reduced IL-8 mRNA and protein levels and inhibited KS cell growth in a dose-dependent manner. In addition, supernatant from a KS cell line induced the growth of HUVECs and angiogenesis in chicken chorioallantoic membrane assays, both of which were inhibited by IL-8 neutralizing antibody. Serum levels of IL-8 were also elevated in KS cases compared with matched controls. Modulation of IL-8 may thus be of therapeutic value in this disease.
 ...
PMID:Interleukin 8 is an autocrine growth factor and a surrogate marker for Kaposi's sarcoma. 1155 81

Human immunodeficiency virus (HIV)-1 Nef protein is an essential modulator of AIDS pathogenesis and we have previously demonstrated that rNef enters uninfected human monocytes and induces T cells bystander activation, up-regulating IL-15 production. Since dendritic cells (DCs) play a central role in HIV-1 primary infection we investigated whether rNef affects DCs phenotypic and functional maturation in order to define its role in the immunopathogenesis of AIDS. We found that rNef up-regulates the expression on immature DCs of surface molecules known to be critical for their APC function. These molecules include CD1a, HLA-DR, CD40, CD83, CXCR4, and to a lower extent CD80 and CD86. On the other hand, rNef down-regulates surface expression of HLA-ABC and mannose receptor. The functional consequence of rNef treatment of immature DCs is a decrease in their endocytic and phagocytic activities and an increase in cytokine (IL-1beta, IL-12, IL-15, TNF-alpha) and chemokine (MIP-1alpha, MIP-1beta, IL-8) production as well as in their stimulatory capacity. These results indicate that rNef induces a coordinate series of phenotypic and functional changes promoting DC differentiation and making them more competent APCs. Indeed, Nef induces CD4(+) T cell bystander activation by a novel mechanism involving DCs, thus promoting virus dissemination.
 ...
PMID:HIV-1 Nef induces dendritic cell differentiation: a possible mechanism of uninfected CD4(+) T cell activation. 1196 93

The brain is a target organ for recreational drugs and HIV-1. Epidemiological data demonstrate that opioid abuse is a risk factor for HIV-1 infection and progression to AIDS. Chemokines and their receptors have been implicated in the neuropathogenesis of HIV-1 infections. However, little is known about the effects of opioids on the expression of chemokines and their receptors (the latter also are HIV-1 coreceptors) by cells of the CNS. Herein we describe the effects of morphine on gene expression of the alpha- and beta-chemokines and their receptors by the astrocytoma cell line U87 and by primary normal human astrocyte (NHA) cultures. U87 cells treated with morphine showed significant down-regulation of IL-8 gene expression, whereas expression of the IL-8 receptor CXCR2 was reciprocally up-regulated as detected by RT-PCR. Treatment of NHAs with morphine suppressed IL-8 and macrophage-inflammatory protein-1beta gene expression, whereas expression of their receptor genes, CCR3 and CCR5, was simultaneously enhanced. These morphine-induced effects on U87 and NHA cells were reversed by the opioid mu receptor antagonist beta-funaltrexamine. Morphine also enhanced the constitutive expression of the opioid mu receptor on astroglial cells. Our results support the hypothesis that opioids play a significant role in the susceptibility of the CNS to HIV-1 infection and subsequent encephalopathy by inhibiting local production of HIV-1-protective chemokines (IL-8 and macrophage-inflammatory protein-1beta) and enhancing expression of HIV-1 entry coreceptor genes (CCR3, CCR5, and CXCR2) within the CNS. These effects of opioids appear to be mediated through the opioid mu receptor that we demonstrated on astroglial cells.
 ...
PMID:Morphine regulates gene expression of alpha- and beta-chemokines and their receptors on astroglial cells via the opioid mu receptor. 1224 49

Two common features in human immunodeficiency virus infection and acquired immunodeficiency syndrome, rheumatoid arthritis, and hematologic malignancies including multiple myeloma are elevated serum levels of beta(2)-microglobulin (beta(2)M) and activation or inhibition of the immune system. We hypothesized that beta(2)M at high concentrations may have a negative impact on the immune system. In this study, we examined the effects of beta(2)M on monocyte-derived dendritic cells (MoDCs). The addition of beta(2)M (more than 10 microg/mL) to the cultures reduced cell yield, inhibited the up-regulation of surface expression of human histocompatibility leukocyte antigen (HLA)-ABC, CD1a, and CD80, diminished their ability to activate T cells, and compromised generation of the type-1 T-cell response induced in allogeneic mixed-lymphocyte reaction. Compared with control MoDCs, beta(2)M-treated cells produced more interleukin-6 (IL-6), IL-8, and IL-10. beta(2)M-treated cells expressed significantly fewer surface CD83, HLA-ABC, costimulatory molecules, and adhesion molecules and were less potent at stimulating allospecific T cells after an additional 48-hour culture in the presence of tumor necrosis factor-alpha and IL-1beta. During cell culture, beta(2)M down-regulated the expression of phosphorylated mitogen-activated protein (MAP) kinases, extracellular signal-related kinase (ERK), and mitogen-induced extracellular kinase (MEK), inhibited nuclear factor-kappaB (NF-kappaB), and activated signal transducer and activator of transcription-3 (STAT3) in treated cells, all of which are involved in cell differentiation and proliferation. Thus, our study demonstrates that beta(2)M at high concentrations retards the generation of MoDCs, which may involve down-regulation of major histocompatibility complex class I molecules, inactivation of Raf/MEK/ERK cascade and NF-kappaB, and activation of STAT3, and it merits further study to elucidate the underlying mechanisms.
 ...
PMID:Beta 2-microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells. 1253 97


<< Previous 1 2 3 4 5 6 7 8 9 Next >>