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)

We have investigated the expression of chemokines and their receptors in leprosy skin lesions using immunohistochemistry. Skin biopsies from 25 leprosy patients across the leprosy spectrum, 11 patients undergoing type I reversal reactions and four normal donors were immunostained by ABC peroxidase method using antibodies against CC and CXC chemokines and their receptors. Using an in situ hybridization technique we have also studied the expression of monocyte chemoattractant protein 1 (MCP-1), RANTES and interleukin (IL)-8 chemokines mRNA in leprosy skin lesions. Chemokines and receptor expression was detected in all leprosy skin biopsies. Expression of CC chemokines MCP-1 (P < 0.01) and RANTES (P < 0.01) were elevated significantly in borderline tuberculoid leprosy in reversal reaction compared to non-reactional borderline tuberculoid leprosy, but there was no difference in the expression of IL-8 chemokine. Surprisingly, there was no significant difference in the expression of CC (CCR2 and CCR5) and CXC (CXCR2) chemokine receptors across the leprosy spectrum. Similarly, there was no significant difference in the expression of mRNA for MCP-1, regulated upon activation normal T cell expressed and secreted (RANTES) and IL-8 chemokines. Here, the presence of a neutrophil chemoattractant IL-8 in leprosy lesions, which do not contain neutrophils, suggests strongly a role of IL-8 as a monocyte and lymphocyte recruiter in leprosy lesions. These results suggest that the chemokines and their receptors, which are known to chemoattract T lymphocytes and macrophages, are involved in assembling the cellular infiltrate found in lesions across the leprosy spectrum.
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PMID:Expression of CC and CXC chemokines and chemokine receptors in human leprosy skin lesions. 1463 50

Within the brain, quinolinic acid (QUIN) is an important neurotoxin, especially in AIDS dementia complex (ADC). Its production by monocytic lineage cells is increased in the context of inflammation. However, it is not known whether QUIN promotes inflammation. Astrocytes are important in immuno-regulation within the brain and so we chose to examine the effects of QUIN on the astrocyte. Using purified cultures of primary human foetal astrocyte, we determined chemokine production using ELISA assays and RT-PCR, and chemokine receptor expression using immunocytochemistry and RT-PCR with QUIN in comparison to TNF-alpha/IFN-gamma. We found that QUIN induces astrocytes to produce large quantities of MCP-1 (CCL2), and lesser amounts of RANTES (CCL5), IL-8 (CXCL8). QUIN also increases SDF-1alpha (CXCL12), HuMIG (CXCL9) and fractalkine (CX3CL1) mRNA expression. Moreover, QUIN leads to up-regulation of the chemokine receptor expression of CXCR4, CCR5, and CCR3 in human foetal astrocytes. Most of these effects were comparable to those induced by TNF-alpha/IFN-gamma. The present work represents the first evidence that QUIN induces chemokine and chemokine receptor expression in astrocytes and is at least as potent as classical mediators such as inflammatory cytokines. These results suggest that QUIN may be critical in the amplification of brain inflammation particularly in ADC.
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PMID:Quinolinic acid up-regulates chemokine production and chemokine receptor expression in astrocytes. 1520 14

Solid tumour and leukemic cells expressing chemokine receptors, metastasize to chemokine-secreting organs. Chemokines indirectly affect tumour development by attracting immunocompetent cells with pro- or anti-tumoral activities. Various membrane-associated and soluble proteases selectively cleave specific chemokines. Precursor plasma chemokines (CXCL7, CCL14) need to be proteolytically processed to obtain receptor affinity. Angiogenic CXC chemokines (CXCL1, CXCL8) have increased CXCR1/CXCR2 affinity after limited NH2-terminal processing, whereas truncated angiostatic chemokines (CXCL10) show lower CXCR3 affinity without loss of angiostatic potential. NH2-terminally cleaved monocyte chemotactic proteins (CCL2, CCL7, CCL8) have impaired capacity to attract tumour-associated macrophages and function as receptor antagonists for intact CC chemokines. Migration of Th1/CCR5+ and Th2/CCR4+ effector lymphocytes toward CCR5 (CCL5, CCL3L1) and CCR4 (CCL22) ligands is affected by cleavage. Although proteolytical processing of chemokines is well studied in vitro, the direct or indirect effects on tumour invasion and metastasis are only poorly evaluated.
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PMID:Chemokine-protease interactions in cancer. 1524 56

The filoviruses, Ebola (EBOV) and Marburg (MARV), are potential global health threats, which cause deadly hemorrhagic fevers. Although both EBOV and MARV logarithmically replicate in dendritic cells (DCs), these viruses do not elicit DC cytokine secretion and fail to activate and mature infected DCs. Here, we employed virus-like particles (VLPs) of EBOV and MARV to investigate whether these genome-free particles maintain similar immune evasive properties as authentic filoviruses. Confocal microscopy indicated that human myeloid-derived DCs readily took up VLPs. However, unlike EBOV and MARV, VLPs induced maturation of DCs including upregulation of costimulatory molecules (CD40, CD80, CD86), major histocompatibility complex (MHC) class I and II surface antigens, and the late DC maturation marker CD83. The chemokine receptors CCR5 and CCR7 were also modulated on VLP-stimulated DCs, indicating that DC could migrate following VLP exposure. Furthermore, VLPs also elicited DC secretion of the pro-inflammatory cytokines TNF-alpha, IL-8, IL-6, and MIP-1alpha. Most significantly, in stark contrast to DC treated with intact EBOV or MARV, DC stimulated with EBOV or MARV VLPs showed enhanced ability to support human T-cell proliferation in an allogenic mixed lymphocyte response (MLR). Thus, our findings suggest that unlike EBOV and MARV, VLPs are effective stimulators of DCs and have potential in enhancing innate and adaptive immune responses.
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PMID:Ebola and Marburg virus-like particles activate human myeloid dendritic cells. 1530 13

Toll-like receptor 2 (TLR2) stimulation in monocytes may contribute to enhanced inflammation and viral replication in HIV infection. In the present study we examined if TLR2 stimulation could modulate chemokine responses in peripheral blood mononuclear cells (PBMC) from HIV-infected patients and healthy controls. Our main findings were, with similar qualitative patterns in both healthy controls and HIV-infected patients: (1) TLR2 stimulation induced up-regulation of several chemokines at the mRNA level as well as increased protein levels of macrophage inflammatory protein (MIP)-1alpha, interleukin (IL)-8 and regulated on activation, normal T cell expressed and secreted (RANTES); (2) TLR2 stimulation induced enhanced protein expression of CCR5 (a receptor for MIP-1alpha and RANTES) on monocytes; (3) In vitro stimulation with RANTES induced release of MIP-1alpha, MCP-1, IL-8 and interferon-gamma from PBMC. While increased levels of beta-chemokines possibly have antiviral effects, TLR2 stimulation may also promote a chemokine-driven inflammatory loop, potentially contributing to the immunopathogenesis of HIV infection.
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PMID:Stimulation of toll-like receptor 2 in mononuclear cells from HIV-infected patients induces chemokine responses: possible pathogenic consequences. 1537 13

CCL3 (MIP-1alpha), a prototype of CC chemokines, is a potent chemoattractant toward human neutrophils pre-treated with GM-CSF for 15 min. GM-CSF-treated neutrophils migrate also to the selective CCR5 agonist CCL4 (MIP-1beta). CCL3- and CCL4-triggered migration of GM-CSF-primed neutrophils was inhibited by the CCR5 antagonist TAK-779. Accordingly, freshly isolated neutrophils express CCR5. Extracellular signal-regulated kinases (ERK)-1/2 and p38 mitogen-activated protein kinase (MAPK) inhibitors blocked CCL3-induced migration of GM-CSF-primed neutrophils. When the activation of ERK-1/2 and p38 MAPK by CCL3 and the classical neutrophilic chemokine CXCL8 (IL-8) were compared, both the chemokines were capable of activating p38 MAPK. On the contrary, whereas both ERK-1 and ERK-2 were activated by CXCL8, no ERK-1 band was detectable after CCL3 triggering. Finally, neutrophil pre-treatment with GM-CSF activated both ERK-1 and ERK-2. This suggests that by activating ERK-1, GM-CSF renders neutrophils rapidly responsive to CCL3 stimulation throughout CCR5 which is constitutively expressed on the cell surface.
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PMID:CCL3 (MIP-1alpha) induces in vitro migration of GM-CSF-primed human neutrophils via CCR5-dependent activation of ERK 1/2. 1556 66

Epidemiological studies show reduced risk of Alzheimer's disease (AD) among patients using non-steroidal inflammatory drugs (NSAID) indicating the role of inflammation in AD. Studies have shown a chronic CNS inflammatory response associated with increased accumulation of amyloid peptide and activated microglia in AD. Our previous studies showed that interaction of Abeta1-40 or fibrilar Abeta1-42 caused activation of nuclear transcription factor, early growth response-1 (Egr-1), which resulted in increased expression of cytokines (TNF-alpha and IL-1beta) and chemokines (MIP-1beta, MCP-1 and IL-8) in monocytes. We determined whether curcumin, a natural product known to have anti-inflammatory properties, suppressed Egr-1 activation and concomitant expression of cytochemokines. We show that curcumin (12.5-25 microm) suppresses the activation of Egr-1 DNA-binding activity in THP-1 monocytic cells. Curcumin abrogated Abeta1-40-induced expression of cytokines (TNF-alpha and IL-1beta) and chemokines (MIP-1beta, MCP-1 and IL-8) in both peripheral blood monocytes and THP-1 cells. We found that curcumin inhibited Abeta1-40-induced MAP kinase activation and the phosphorylation of ERK-1/2 and its downstream target Elk-1. We observed that curcumin inhibited Abeta1-40-induced expression of CCR5 but not of CCR2b in THP-1 cells. This involved abrogation of Egr-1 DNA binding in the promoter of CCR5 by curcumin as determined by: (i) electrophoretic mobility shift assay, (ii) transfection studies with truncated CCR5 gene promoter constructs, and (iii) chromatin immunoprecipitation analysis. Finally, curcumin inhibited chemotaxis of THP-1 monocytes in response to chemoattractant. The inhibition of Egr-1 by curcumin may represent a potential therapeutic approach to ameliorate the inflammation and progression of AD.
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PMID:Curcumin, the active constituent of turmeric, inhibits amyloid peptide-induced cytochemokine gene expression and CCR5-mediated chemotaxis of THP-1 monocytes by modulating early growth response-1 transcription factor. 1556 63

Phagocytosis of inhaled Bacillus anthracis spores and subsequent trafficking to lymph nodes are decisive events in the progression of inhalational anthrax because they initiate germination and dissemination of spores. Found in high frequency throughout the respiratory track, dendritic cells (DCs) routinely take up foreign particles and migrate to lymph nodes. However, the participation of DCs in phagocytosis and dissemination of spores has not been investigated previously. We found that human DCs readily engulfed fully pathogenic Ames and attenuated B. anthracis spores predominately by coiling phagocytosis. Spores provoked a loss of tissue-retaining chemokine receptors (CCR2, CCR5) with a concurrent increase in lymph node homing receptors (CCR7, CD11c) on the membrane of DCs. After spore infection, immature DCs displayed a mature phenotype (CD83(bright), HLA-DR(bright), CD80(bright), CD86(bright), CD40(bright)) and enhanced costimulatory activity. Surprisingly, spores activated the MAPK cascade (ERK, p38) within 30 min and stimulated expression of several inflammatory response genes by 2 h. MAPK signaling was extinguished by 6 h infection, and there was a dramatic reduction of secreted TNF-alpha, IL-6, and IL-8 in the absence of DC death. This corresponded temporally with enzymatic cleavage of proximal MAPK signaling proteins (MEK-1, MEK-3, and MAP kinase kinase-4) and may indicate activity of anthrax lethal toxin. Taken together, these results suggest that B. anthracis may exploit DCs to facilitate infection.
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PMID:Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax pathogenesis. 1584 53

The IL-8 (or CXCL8) chemokine receptors, CXCR1 and CXCR2, activate protein kinase C (PKC) to mediate leukocyte functions. To investigate the roles of different PKC isoforms in CXCL8 receptor activation and regulation, human mononuclear phagocytes were treated with CXCL8 or CXCL1 (melanoma growth-stimulating activity), which is specific for CXCR2. Plasma membrane association was used as a measure of PKC activation. Both receptors induced time-dependent association of PKCalpha, -beta1, and -beta2 to the membrane, but only CXCR1 activated PKCepsilon. CXCL8 also failed to activate PKCepsilon in RBL-2H3 cells stably expressing CXCR2. DeltaCXCR2, a cytoplasmic tail deletion mutant of CXCR2 that is resistant to internalization, activated PKCepsilon as well as CXCR1. Expression of the PKCepsilon inhibitor peptide epsilonV1 in RBL-2H3 cells blocked PKCepsilon translocation and inhibited receptor-mediated exocytosis, but not phosphoinositide hydrolysis or peak intracellular Ca(2+) mobilization. epsilonV1 also inhibited CXCR1-, CCR5-, and DeltaCXCR2-mediated cross-regulatory signals for GTPase activity, Ca(2+) mobilization, and internalization. Peritoneal macrophages from PKCepsilon-deficient mice (PKCepsilon(-/-)) also showed decreased CCR5-mediated cross-desensitization of G protein activation and Ca(2+) mobilization. Taken together, the results indicate that CXCR1 and CCR5 activate PKCepsilon to mediate cross-inhibitory signals. Inhibition or deletion of PKCepsilon decreases receptor-induced exocytosis and cross-regulatory signals, but not phosphoinositide hydrolysis or peak intracellular Ca(2+) mobilization, suggesting that cross-regulation is a Ca(2+)-independent process. Because DeltaCXCR2, but not CXCR2, activates PKCepsilon and cross-desensitizes CCR5, the data further suggest that signal duration leading to activation of novel PKC may modulate receptor-mediated cross-inhibitory signals.
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PMID:Cross-desensitization among CXCR1, CXCR2, and CCR5: role of protein kinase C-epsilon. 1590 35

Little is known about the regulation and coordinated expression of genes involved in the innate host response to Candida albicans. We therefore examined the kinetic profile of gene expression of innate host defense molecules in normal human monocytes infected with C. albicans using microarray technology. Freshly isolated peripheral blood monocytes from five healthy donors were incubated with C. albicans for 0 to 18 h in parallel with time-matched uninfected control cells. RNA from monocytes was extracted and amplified for microarray analysis, using a 42,421-gene cDNA chip. Expression of genes encoding proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 (IL-1), IL-6, and leukemia inhibitory factor, was markedly enhanced during the first 6 h and coincided with an increase in phagocytosis. Expression of these genes returned to near baseline by 18 h. Genes encoding chemokines, including IL-8; macrophage inflammatory proteins 1, 3, and 4; and monocyte chemoattractant protein 1, also were strongly up-regulated, with peak expression at 4 to 6 h, as were genes encoding chemokine receptors CCR1, CCR5, CCR7, and CXCR5. Expression of genes whose products may protect monocyte viability, such as BCL2-related protein, metallothioneins, CD71, and SOCS3, was up-regulated at 4 to 6 h and remained elevated throughout the 18-h time course. On the other hand, expression of genes encoding T-cell-regulatory molecules (e.g., IL-12, gamma interferon, and transforming growth factor beta) was not significantly affected during the 18-h incubation. Moreover, genes encoding IL-15, the IL-13 receptor (IL-13Ra1), and CD14 were suppressed during the 18-h exposure to C. albicans. Thus, C. albicans is a potent inducer of a dynamic cascade of expression of genes whose products are related to the recruitment, activation, and protection of neutrophils and monocytes.
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PMID:Expression of genes encoding innate host defense molecules in normal human monocytes in response to Candida albicans. 1590 1


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