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

The role of chemokines and their receptors in HIV biology and Kaposi's sarcoma (KS) pathogenesis has recently gained considerable attention. It has been shown that KS-associated human herpes virus type 8 (KSHV/HHV-8) encodes functional homologues of certain chemokines and chemokine receptors. This suggests that chemokines may contribute to the growth and spread of KS seen in AIDS. We found the expression of CXCR4 in primary KS tissue by using in situ hybridization (ISH). Recently, alpha-chemokine receptors CXCR1 and CXCR2 have also been shown to be expressed by KS tissues. We further characterized the expression of these chemokines as well as the signaling events induced upon binding to their respective cognate ligands in the KS 38 spindle cell line. These cells express authentic characteristics of primary KS spindle cells and provide a useful in vitro model for these studies. We observed using RT-PCR that KS 38 cells express mRNA for the alpha-chemokine receptors CXCR1, CXCR2, and CXCR4. We also confirmed the cell surface protein expression by FACS analysis. Characterization of signaling pathways revealed that the alpha-chemokines, IL-8 and stromal cell-derived factor 1alpha (SDF1alpha/CXCL12), activated members of the mitogen-activated protein (MAP) kinase family, including Erk kinase, c-Jun amino terminal kinase (JNK)/stress-activated protein kinase (SAPK) and the p38 MAP kinase. Furthermore, using DNA protein-binding experiments, we have shown that IL-8 increased AP-1 and NF Kappa B activity in these cells. IL-8 also enhanced the chemotaxis of KS cells. These results reveal that chemokine-induced signaling pathways may mediate cell growth, transcriptional activation and cell migration in KS.
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PMID:Alpha-chemokine-mediated signal transduction in human Kaposi's sarcoma spindle cells. 1511 Sep 93

In a case-control study, we studied the effect of a single nucleotide polymorphism in the IL-8 promoter on the risk of the development of AIDS-related Kaposi's sarcoma (KS). KS developed in 46% of individuals with the TT genotype and in 66% of AA/AT genotypes (P=0.038). Patients with TT genotype were rarely affected with visceral KS (7% versus 36%; P=0.06), which suggests that carriers of the TT genotype are protected from (severe) KS development.
AIDS 2004 May 21
PMID:An IL-8 gene promoter polymorphism is associated with the risk of the development of AIDS-related Kaposi's sarcoma: a case-control study. 1516 38

Interleukin-8 (IL-8) is the predominant cytokine expressed in the female genital tract of women with certain infectious/inflammatory conditions. IL-8 increased HIV-1 replication in T cells and to a greater extent in monocytes/macrophages in vitro. Physiological levels of IL-8 increased susceptibility to HIV-1 infection 5- to 8-fold in cervical explant tissues. Competitive inhibition of the IL-8 receptor CXCR2 with the small molecule inhibitor SB225002 resulted in a 45-70% decrease in cervical explant susceptibility to HIV-1 infection.
AIDS Res Hum Retroviruses 2005 Mar
PMID:IL-8 increases transmission of HIV type 1 in cervical explant tissue. 1579 29

N-acetyl-L-cysteine (NAC) has been proposed as an additional therapeutic agent for AIDS patients because it reduces human immunodeficiency virus type 1 (HIV-1) replication in stimulated CD4+ lymphocytes, and it ameliorates immunological reactivity. In a randomized, 180-day, double-blind, placebo-controlled trial performed with HIV-infected patients classified as A2 and A3 according to the criteria of the Center for Disease Control and Prevention, we investigated the effects of oral administration of NAC on HIV-infected patients undergoing their first anti-retroviral therapy; viral load, CD4+ lymphocyte, lymphocyte viability and apoptosis, and TNF-alpha and IL-8 levels were determined. Sixteen patients who received anti-retroviral therapy plus a placebo formed the control group and the study group consisted of 14 patients who received anti-retroviral therapy and NAC supplementation. A significant decrease was seen in viral load, TNF-alpha and IL-8 levels, and lymphocyte apoptosis, and a significant increase was found in levels of CD4+ lymphocytes and lymphocyte viability in both groups after anti-retroviral treatment, but no measurable benefits of anti-retroviral therapy plus NAC oral supplementation (600 mg/day) were found in relation to anti-retroviral therapy alone, and the baseline levels of cysteine and glutathione in plasma were not recovered by this treatment. In conclusion, the daily doses of NAC necessary for the total recuperation of plasma cysteine and glutathione levels in HIV-infected patients and the additional benefits following the supplementation of NAC in patients submitted to anti-retroviral therapy, need to be studied further.
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PMID:Effect of N-acetyl-L-cysteine on lymphocyte apoptosis, lymphocyte viability, TNF-alpha and IL-8 in HIV-infected patients undergoing anti-retroviral treatment. 1579 12

There is a growing interest in the role of chemokines and their receptors in the determination of mast cell tissue localization and how chemokines regulate mast cell function. At least nine chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CX3CR1, CCR1, CCR3, CCR4 and CCR5) have been described to be expressed by human mast cells of different origins. Seven chemokines (CXCL1, CXCL5, CXCL8, CXCL14, CX3CL1, CCL5 and CCL11) have been shown to act on some of these receptors and to induce mast cell migration. Mast cells have a unique expression pattern of CCR3, CXCR1 and CXCR2. These receptors are mainly expressed intracellularly on cytoplasmic membranes. Upon an allergic activation, CCR3 expression is increased on the cell surface and the cell becomes vulnerable for CCL11 treatment. Chemokines do not induce mast cell degranulation but CXCL14 causes secretion of de novo synthesized CXCL8. Because of the expression of CCR3, CCR5 and CXCR4 on mast cell progenitors, these cells are susceptible to HIV infection and mast cells might therefore be a persistent HIV reservoir in AIDS. In this review, we summarize the knowledge about chemokine receptor expression and function on mast cells.
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PMID:Chemokine receptor expression by mast cells. 1610 68

Kaposi's sarcoma is multifactorial, involving Kaposi's sarcoma-associated herpesvirus (KSHV) infection and immune dysfunction. A KSHV protein (vOX2), fused with the Fc domain of human immunoglobulin G1 to create vOX2:Fc, suppressed neutrophil oxidative burst and inhibited the production of pro-inflammatory chemokines (IL-8 and monocyte chemoattractant protein 1) by monocyte/macrophage cells. vOX2:Fc suppressed the acute inflammatory response in mice in which neutrophil-mediated inflammation was induced by carrageenan. The data suggest that vOX2 can contribute to immune dysfunction and could have anti-inflammatory therapeutic potential.
AIDS 2005 Nov 04
PMID:Inhibition of neutrophil function by the Kaposi's sarcoma-associated herpesvirus vOX2 protein. 1622 99

Nuclear factor-kappa B (NF-kappaB) is a transcription factor that resides in the cytoplasm of every cell and translocates to the nucleus when activated. Its activation is induced by a wide variety of agents including stress, cigarette smoke, viruses, bacteria, inflammatory stimuli, cytokines, free radicals, carcinogens, tumor promoters, and endotoxins. On activation, NF-kappaB regulates the expression of almost 400 different genes, which include enzymes (e.g., COX-2, 5-LOX, and iNOS), cytokines (such as TNF, IL-1, IL-6, IL-8, and chemokines), adhesion molecules, cell cycle regulatory molecules, viral proteins, and angiogenic factors. The constitutive activation of NF-kappaB has been linked with a wide variety of human diseases, including asthma, atherosclerosis, AIDS, rheumatoid arthritis, diabetes, osteoporosis, Alzheimer's disease, and cancer. Several agents are known to suppress NF-kappaB activation, including Th2 cytokines (IL-4, IL-13, and IL-10), interferons, endocrine hormones (LH, HCG, MSH, and GH), phytochemicals, corticosteroids, and immunosuppressive agents. Because of the strong link of NF-kappaB with different stress signals, it has been called a "smoke-sensor" of the body.
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PMID:Transcription factor NF-kappaB: a sensor for smoke and stress signals. 1638 90

Tuberculosis is the most frequent coinfection in humans infected with HIV-1, but little is known about mechanisms that favors coinfection. The aim of this work is to understand tuberculosis and HIV infections. We determined the pattern of expression of CD11c, CD14, CD40, CCR5, and CXCR4 and quantified IL-1beta, IL-6, IL-8, TNF-alpha, and RANTES in tuberculosis patients and HIV patients. Monocytes from healthy PPD+ volunteers (HP(+)V) stimulated with intracellular proteins (IP), lipids, and polysaccharides (PLS) from Mycobacterium tuberculosis down regulate CD11c expression (p < 0.05). On the contrary, CD14 expression was elevated in tuberculosis patients (p < 0.05) and HIV-infected patients (p > 0.05). CD14 expression was elevated on monocytes from HP(+)V stimulated with PLS and lipids (p < 0.05). CD40 low expression was found in tuberculosis patients and on monocytes from HP(+)V stimulated with lipids, but it was elevated in HIV-infected patients (p < 0.05). CXCR4 and CCR5 expression was high in pulmonary tuberculosis patients and low in HIV-infected patients (p < 0.05). Finally, CCR5+ monocytes from HP(+)V after stimulation with PLS and CXCR4+ lymphocytes were elevated after stimulation with IP (p < 0.05). In general, high levels of IL-1beta, IL-6, and TNF-alpha were found in all groups, but low levels of RANTES were found in pulmonary tuberculosis patients. In conclusion, the pulmonary tuberculosis patients have a microenvironment that facilitates the HIV infection through three possible mechanisms: (1) increasing the coreceptor for HIV entrance, (2) increasing proinflammatory cytokines, and (3) down-regulating RANTES. At the same time, HIV patients have a microenvironment that facilitates entry of M. tuberculosis into macrophages through CD14.
AIDS Res Hum Retroviruses 2006 Jan
PMID:Mycobacterium tuberculosis upregulates coreceptors CCR5 and CXCR4 while HIV modulates CD14 favoring concurrent infection. 1643 45

Cytokines regulate cellular immune activity and are produced by a variety of cells, especially lymphocytes, monocytes, and macrophages. Measurement of cytokine levels has yielded useful information on the pathological process of different diseases such as AIDS, endotoxic shock, sepsis, asthma, and cancer. It may also be of use in the monitoring of disease progression and/or inflammation. To determine spontaneous cytokine gene expression in whole blood and PBMCs, whole blood was obtained from healthy volunteers and total mRNA was isolated from PBMCs. The kinetics of response were determined by sequential testing of cytokine gene expression by RT-PCR analysis. Our results demonstrated that isolated and incubated PBMCs expressed TNF-alpha and high levels of IL-1beta, IL-6, IL-8, and IL-10. In contrast, WB only expressed the mRNA cytokines of TNF-alpha and IL-8 (p < 0.05). These results suggest that spontaneous myriad mRNA cytokine expression can be avoided with the use of WB incubation and the rapid collection of PBMCs. Furthermore, this method should be employed in all cases where the levels of cytokine gene expression can be evaluated.
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PMID:Spontaneous inflammatory cytokine gene expression in normal human peripheral blood mononuclear cells. 1656 5

Human herpesvirus 6 (HHV-6) frequently reactivates in human immunodeficiency virus 1 (HIV-1) infected patients, and is thought to be a cofactor in AIDS progression. Macrophages are targets and reservoirs of HIV-1 and HHV-6; hence, they have an important role in dissemination and pathogenesis of these viruses. The present study examined the effects of HHV-6 A variant on replication of R5 variants of HIV-1 in macrophages. For this purpose, HIV-1 replication was investigated in macrophages infected with HIV-1 alone or along with HHV-6A. Our results demonstrated that HHV-6A significantly suppressed HIV-1 replication in coinfected cultures. HHV-6A infection resulted in increased secretion of RANTES and IL-8. Experiments with exogenous RANTES and IL-8 revealed that these chemokines also significantly suppressed HIV-1 replication in infected macrophages. RANTES is able to induce desensitization and internalization of CCR5, the chemokine coreceptor of R5 variants. In addition, IL-8 receptor activation results in cross-desensitization and cross-internalization of CCR5. We found that CCR5 sensitivity and expression level is diminished in HHV-6A-infected macrophage cultures compared with uninfected cells. Taken together, our results indicate that HHV-6A infection decreases the susceptibility of macrophages to R5 variants of HIV-1 in which the HHV-6A induced RANTES and IL-8 may have importance.
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PMID:Human herpesvirus 6A decreases the susceptibility of macrophages to R5 variants of human immunodeficiency virus 1: possible role of RANTES and IL-8. 1681 83


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