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)

Amino acid deletion and mutagenesis experiments have indicated that the sequences Glu-Leu-Arg (ELR) preceding the first cysteine at the N terminus of interleukin 8 (IL-8) is required for receptor binding and neutrophil activation. Platelet factor 4 (PF4) is structurally related to IL-8 (35% sequence identity) but lacks the N-terminal ELR sequence and comparable effects on neutrophils. We introduced the ELR sequence at the N terminus of PF4 and found that the modified protein was a potent neutrophil activator and attractant. On the other hand, when the ELR sequence was introduced into the corresponding positions of two other proteins related to IL-8, gamma-interferon-inducible protein IP10 and monocyte chemoattractant protein 1, neither of them acquired neutrophil-activating properties, indicating that besides ELR additional structural determinants of IL-8 and PF4 are important for binding to IL-8 receptors. The conservation of these binding determinants suggests that PF4 may have evolved from a neutrophil activating protein.
 ...
PMID:Platelet factor 4 binds to interleukin 8 receptors and activates neutrophils when its N terminus is modified with Glu-Leu-Arg. 847 6

Chemotactic cytokines (chemokines) play an important role in the recruitment of lymphocytes to tissue by regulating cellular adhesion and transendothelial migration. This study examined the expression and function of CXC (human monokine induced by gamma-interferon [HuMig], interleukin-8 [IL-8], and interferon-inducible protein-10 [IP-10]) and CC (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, regulated upon activation normal T lymphocyte expressed and secreted (RANTES), and macrophage chemoattractant protein-1 [MCP-1]) chemokines and their respective receptors on lymphocytes infiltrating human liver tumors. Chemokine and chemokine receptor expression was assessed by immunohistochemistry, flow cytometry, in situ hybridization and ribonuclease (RNAse) protection assays and function by in vitro chemotaxis of tumor-derived lymphocytes to purified chemokines and to HepG2 tumor cell culture supernatants. Tumor-derived lymphocytes showed strong chemotactic responses to both CC and CXC chemokines in vitro and expressed high levels of CXCR3 (HuMig and IP-10 receptor) and CCR5 (RANTES, MIP-1alpha, and MIP-1beta receptor). Expansion of tumor-derived lymphocytes in recombinant IL-2 increased expression of CXCR3. The corresponding chemokines were detected on vascular endothelium (HuMig, IL-8, MIP-1alpha, and MIP-1beta) and sinusoidal endothelium (HuMig, MIP-1alpha, MIP-1beta) in hepatocellular carcinoma. In vitro, HepG2 cells secreted functional chemotactic factors for tumor-derived lymphocytes that could be inhibited using anti-CCR5 or anti-CXCR3 monoclonal antibodies (MoAbs). Thus, lymphocytes infiltrating human liver tumors express receptors for and respond to both CXC and CC chemokines. The relevant chemokine ligands are expressed in hepatocellular carcinoma (HCC), particularly HuMig, which was strongly expressed by tumor endothelium, suggesting that they play a role in lymphocyte recruitment to these tumors in vivo. The ability of HepG2 cells to secrete lymphocyte chemotactic factors in vitro suggests that the tumor contributes to lymphocyte recruitment in vivo.
 ...
PMID:Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma. 1038 45

Levels of interleukin 8 (IL-8), gamma interferon-inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1beta (MIP-1beta) were elevated in patients with tuberculosis. IP-10 and MCP-1 levels were higher in human immunodeficiency virus (HIV)-seropositive patients than in HIV-seronegative patients with tuberculosis. Lipoarabinomannan induced IL-8, MCP-1, and MIP-1beta in vitro, which was partly inhibited by anti-tumor necrosis factor antibody.
 ...
PMID:Elevated chemokine concentrations in sera of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients with tuberculosis: a possible role for mycobacterial lipoarabinomannan. 1041 9

The basis for the angiogenic effects of CXC chemokines such as interleukin 8 (IL-8) and for angiostatic chemokines such as interferon-inducible protein 10 (IP-10) has been difficult to assess. We recently reported, based on an RNase protection assay, that human umbilical vein endothelial cells (HUVECs) did not express detectable mRNA for the IL-8 receptors CXCR1 and CXCR2. This raised the possibility of heterogeneity of receptor expression by different endothelial cell (ECs) types. Since systemic angiogenesis induced by IL-8 would more likely involve microvessel ECs, we investigated CXC receptor expression on human microvascular dermal endothelial cells (HMECs). By confocal microscopy and immunofluorescence we observed that HMECs consistently expressed high levels of CXCR1 and CXCR4 (mean fluorescence intensity of 261+/-22.1 and 306.2+/-19, respectively) and intermediate levels of CXCR3 and CXCR2 (173.9+/-30. 2 and 156+/-30.9, respectively). In contrast, only a small proportion of HUVEC preparations expressed low levels of CXCR1, -2, and -3 (66+/-19.9; 49+/-15, and 81.4+/-17.9, respectively). However, both HMECs and HUVECs expressed equal levels of CXCR4. As expected, HMECs had more potent chemotactic responses to IL-8 than HUVECs, and this was correlated with the levels of IL-8 receptors on the ECs. Antibodies to CXCR1 and CXCR2 each had inhibitory effects on chemotaxis of HMECs to IL-8, indicating that both IL-8 receptors contributed to the migratory response of these cells toward IL-8. Assessment of the functional capacity of CXCR3 unexpectedly revealed that HMECs migrated in response to relatively higher concentrations (100-500 ng/ml) of each of the 'angiostatic' chemokines IP-10, ITAC, and MIG. Despite this, the 'angiostatic' chemokines inhibited the chemotactic response of HMECs to IL-8. IL-8 and SDF-1alpha but not IP-10 induced calcium mobilization in adherent ECs, suggesting that signaling events associated with calcium mobilization are separable from those required for chemotaxis. Taken together, our data indicated that functional differences among EC types is dependent on the level of the expression of CXC chemokine receptors. Whether this heterogeneity in receptor expression by ECs reflects distinct differentiation pathways remains to be established.
 ...
PMID:Differential expression and responsiveness of chemokine receptors (CXCR1-3) by human microvascular endothelial cells and umbilical vein endothelial cells. 1102 90

Chemokines are inflammatory molecules that act primarily as chemoattractants and as activators of leukocytes. Their role in antigen-specific immune responses is of importance, but their role in disease protection is unknown. Recently it has been suggested that chemokines modulate immunity along more classical Th1 and Th2 phenotypes. However, no data currently exist in an infectious challenge model system. We analyzed the modulatory effects of selected chemokines (interleukin-8 [IL-8], gamma interferon-inducible protein 10 [IP-10], RANTES, monocyte chemotactic protein 1 [MCP-1], and macrophage inflammatory protein 1 alpha [MIP-1 alpha]) on immune phenotype and protection against lethal challenge with herpes simplex virus type 2 (HSV-2). We observed that coinjection with IL-8 and RANTES plasmid DNAs dramatically enhanced antigen-specific Th1 type cellular immune responses and protection from lethal HSV-2 challenge. This enhanced protection appears to be mediated by CD4(+) T cells, as determined by in vitro and in vivo T-cell subset deletion. Thus, IL-8 and RANTES cDNAs used as DNA vaccine adjuvants drive antigen-specific Th1 type CD4(+) T-cell responses, which result in reduced HSV-2-derived morbidity, as well as reduced mortality. However, coinjection with DNAs expressing MCP-1, IP-10, and MIP-1 alpha increased mortality in the challenged mice. Chemokine DNA coinjection also modulated its own production as well as the production of cytokines. These studies demonstrate that chemokines can dominate and drive immune responses with defined phenotypes, playing an important role in the generation of protective antigen-specific immunity.
 ...
PMID:DNA vaccines encoding interleukin-8 and RANTES enhance antigen-specific Th1-type CD4(+) T-cell-mediated protective immunity against herpes simplex virus type 2 in vivo. 1107 14

Using flow cytometric and RNase protection assays, this study examined the expression of chemokine receptors in nonactivated natural killer (NK) cells and compared this expression with NK cells activated with interleukin (IL)-2, which either adhered to plastic flasks (AD) or did not adhere (NA). None of the NK cell subsets expressed CXCR2, CXCR5, or CCR5. The major differences between these cells include increased expression of CXCR1, CCR1, CCR2, CCR4, CCR8, and CX(3)CR1 in AD when compared to NA or nonactivated NK cells. The chemotactic response to the CXC and CC chemokines correlated with the receptor expression except that all 3 populations responded to GRO-alpha, despite their lack of CXCR2 expression. Pretreatment of these cells with anti-CXCR2 did not inhibit the chemotactic response to GRO-alpha. In addition, nonactivated and NA cells responded to fractalkine, although they lack the expression of CX(3)CR1. This activity was not inhibited by anti-CX(3)CR1. Viral macrophage inflammatory protein (vMIP)-I, I-309, and TARC competed with the binding of (125)I-309 to AD cells with varying affinities. Transforming growth factor (TGF)-beta1 but not any other cytokine or chemokine examined including interferon (IFN)-gamma, MIP-3beta, macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC) or I-309, up-regulated the expression of CXCR3 and CXCR4 on NK cell surface. This is correlated with increased chemotaxis of NK cells treated with TGF-beta1 toward stromal cell-derived factor (SDF)-1alpha and interferon-inducible protein-10 (IP-10). Messenger RNA for lymphotactin, RANTES, MIP-1alpha, and MIP-1beta, but not IP-10, monocyte chemotactic protein (MCP)-1, IL-8, or I-309 was expressed in all 3 NK cell subsets. Our results may have implications for the dissemination of NK cells at the sites of tumor growth or viral replication. (Blood. 2001;97:367-375)
 ...
PMID:Expression and regulation of chemokine receptors in human natural killer cells. 1115 10

The aim of this study was to explore further the hypothesis that early stages of normal human hematopoiesis might be coregulated by autocrine/paracrine regulatory loops and by cross-talk among early hematopoietic cells. Highly purified normal human CD34(+) cells and ex vivo expanded early colony-forming unit-granulocyte-macrophage (CFU-GM)-derived, burst forming unit-erythroid (BFU-E)-derived, and CFU-megakaryocyte (CFU-Meg)-derived cells were phenotyped for messenger RNA expression and protein secretion of various growth factors, cytokines, and chemokines to determine the biological significance of this secretion. Transcripts were found for numerous growth factors (kit ligand [KL], FLT3 ligand, fibroblast growth factor-2 [FGF-2], vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF], insulinlike growth factor-1 [IGF-1], and thrombopoietin [TPO]); cytokines (tumor necrosis factor-alpha, Fas ligand, interferon alpha, interleukin 1 [IL-1], and IL-16); and chemokines (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, regulated upon activation, normal T cell expressed and secreted [RANTES], monocyte chemotactic protein-3 [MCP-3], MCP-4, IL-8, interferon-inducible protein-10, macrophage-derived chemokine [MDC], and platelet factor-4 [PF-4]) to be expressed by CD34(+) cells. More importantly, the regulatory proteins VEGF, HGF, FGF-2, KL, FLT3 ligand, TPO, IL-16, IGF-1, transforming growth factor-beta1 (TGF-beta1), TGF-beta2, RANTES, MIP-1alpha, MIP-1beta, IL-8, and PF-4 were identified in media conditioned by these cells. Moreover, media conditioned by CD34(+) cells were found to inhibit apoptosis and slightly stimulate the proliferation of other freshly isolated CD34(+) cells; chemo-attract CFU-GM- and CFU-Meg-derived cells as well as other CD34(+) cells; and, finally, stimulate the proliferation of human endothelial cells. It was also demonstrated that these various hematopoietic growth factors, cytokines, and chemokines are expressed and secreted by CFU-GM-, CFU-Meg-, and BFU-E-derived cells. It is concluded that normal human CD34(+) cells and hematopoietic precursors secrete numerous regulatory molecules that form the basis of intercellular cross-talk networks and regulate in an autocrine and/or a paracrine manner the various stages of normal human hematopoiesis.
 ...
PMID:Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. 1134 33

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.
 ...
PMID:Hantavirus infection induces the expression of RANTES and IP-10 without causing increased permeability in human lung microvascular endothelial cells. 1139 Jun 9

Various cytokines and chemokines play a role in carcinogenesis. However, no study has previously been undertaken to investigate comprehensively the expressions of cytokines and chemokines in hepatoma cells. In this study, we determined which cytokines and chemokines are expressed in hepatoma cells. Recently, it was reported that the expressions of several chemokines could be increased by Fas stimulus in many normal and cancer cells. Therefore, we also investigated whether chemokines expression is regulated by Fas ligation. To address this issue, we performed RNase protection assays upon 13 cytokines and 8 chemokines genes in 10 human hepatoma cell lines, comprising 8 hepatitis B virus (HBV)-associated hepatoma cell lines. Transforming growth factor-beta2 (TGF-beta2) was found to be expressed in 8 HBV-associated hepatoma cell lines, and to be potently expressed in 5 cell lines; however, the mRNA expressions of interleukin-10 (IL-10), IL-12, interferon-gamma(IFN-gamma) and tumor necrosis factor-alpha(TNF-alpha) were not detected in any cell lines examined. Among the chemokines investigated in this study, IL-8 was expressed by 8 HBV- associated hepatoma cell lines, and monocyte chemoattractant protein-1 (MCP-1) by 7 HBV-associated hepatoma cell lines. However, the mRNA expressions of macrophage inflammatory protein-1alpha(MIP-1alpha), MIP-1beta, interferon-inducible protein-10 (IP-10), RANTES, lymphotactin and I-309 were either very weak or undetectable. Fas ligation did not increase chemokines expression in hepatoma cells. Conclusively, TGF-beta2, IL-8 and MCP-1 were overexpressed in HBV-associated hepatoma cells, and the expressions of chemokines were not increased by Fas ligation in human hepatoma cells.
 ...
PMID:Expression patterns of cytokines and chemokines genes in human hepatoma cells. 1240 81

Inducible nitric oxide (NO) synthase (iNOS) appears to be a marker of tumor progression in colon carcinogenesis. Here we investigated effects of NO on selected chemokines that differentially regulate angiogenesis, namely pro-angiogenic interleukin (IL)-8 as well as tumor-suppressive interferon-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG). These chemokines are expressed by DLD-1 colon carcinoma cells after stimulation with IL-1beta/interferon-gamma. Expression of IL-8 was markedly upregulated by NO. Moreover, NO enhanced expression of vascular endothelial growth factor (VEGF). In contrast, expression of IP-10 and MIG was suppressed by NO. The present data are consistent with previous observations that link NO to enhanced tumor angiogenesis and imply that NO-mediated upregulation of IL-8 and VEGF as well as downregulation of IP-10 and MIG may contribute to this phenomenon.
 ...
PMID:Nitric oxide differentially regulates pro- and anti-angiogenic markers in DLD-1 colon carcinoma cells. 1506 30


1 2 3 4 5 Next >>