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)

Neutrophil elicitation into tissue is an essential element of the host defense in response to various stimuli, including, tissue injury, infection, or cancer. This event has gained renewed interest with the discovery of a family of small polypeptides (less than 10 kD). The salient features of these cytokines are the presence of four cysteine amino acids (first two separated by one amino acid; C-X-C) and their ability to induce neutrophil chemotaxis and activation. Recently, our laboratories have discovered a new member of this C-X-C chemotactic cytokine supergene family, neutrophil-activating peptide, ENA-78. ENA-78 shares significant amino acid sequence homology with neutrophil activating peptide-2 (NAP-2; 53%), growth regulated oncogene/melanoma growth stimulatory activity (GRO alpha; 52%), and IL-8 (22%). In addition, ENA-78 appears to activate neutrophils through the IL-8 receptor. Since both in vitro and in vivo biological fluids may contain an array of chemotactic cytokines that may be relevant to the activation and chemotaxis of neutrophils, we have developed a highly specific and sensitive sandwich ELISA for the detection of ENA-78.
 ...
PMID:The detection of a novel neutrophil-activating peptide (ENA-78) using a sensitive ELISA. 142 26

As a preliminary to transducing human melanoma cells with lymphokine genes, we sought for constitutive gene expression and production of eight interleukins, tumour necrosis factors and granulocyte-colony stimulating factor in 19 human melanoma cell lines. Conversion of RNA into cDNA by reverse transcriptase and polymerase chain reaction (RT-PCR) were employed to evaluate gene expression while enzyme-linked immunosorbent assays (ELISA) or biological assays were used to assess the presence of proteins. No expression of interleukins (IL) 3, 4, and 5 or interferon-gamma RNA was found, while the other cytokines were variably expressed in melanoma lines, with IL-1 alpha, IL-1 beta, IL-6, IL-8, being detectable in most of the lines. At protein level, 10 melanoma cells were tested with ELISA and all were found to produce IL-8, five produced IL-6, two tumour necrosis factor (TNF)-alpha, one IL-1 alpha and two TNF beta. The levels of TNF beta were at the limit of test sensitivity. The amount of various cytokines released by the different lines varied widely. Biological assay with the D10-G4 clone confirmed the presence of IL-1 alpha in the supernatant of melanoma (ME) 10221 and revealed an IL-1 activity in the supernatant of Me 4024/1. The proliferating activity of melanoma supernatants on D10-G4 was inhibited by treatment with polyclonal antibodies against IL-1 alpha but not with antibodies against IL-1 beta. TNF biological activity was tested against the TNF-susceptible fibrosarcoma WEHI 164 clone 13.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res 1992 Sep
PMID:Expression of cytokine genes, including IL-6, in human malignant melanoma cell lines. 145 Jun 72

Several structural homologues of the chemotactic peptide neutrophil-activating peptide 1/IL-8 (NAP-1/IL-8) were tested for their ability to influence the expression and function of adhesion-promoting receptors on human polymorphonuclear leukocytes (PMN). NAP-2, melanoma growth stimulatory activity, and two forms of NAP-1/IL-8 (ser-NAP-1/IL-8 and ala-NAP-1/IL-8, consisting of 72 and 77 amino acids, respectively), each caused an increase in the expression of CD11b/CD18 (CR3) and CR1, which was accompanied by a decrease in the expression of leukocyte adhesion molecule-1 (LAM-1, LECAM-1). The binding activity of CD11b/CD18 was also enhanced 3- to 10-fold by these peptides, but enhanced function was transient: binding of erythrocytes coated with C3bi reached a maximum by 30 min and declined thereafter. Ser-NAP-1/IL-8, ala-NAP-1/IL-8, NAP-2, and melanoma growth stimulatory activity also caused a two- to threefold enhancement of the phagocytosis of IgG-coated erythrocytes (EIgG) by PMN without causing a large increase in the expression of Fc gamma receptors. Enhanced phagocytosis of EIgG appeared to be mediated through CD11b/CD18, because F(ab')2 fragments of an antibody directed against CD18 inhibited NAP-1/IL-8-stimulated ingestion of EIgG. The four active peptides caused a rapid, transient increase in the amount of F-actin within PMN, indicating that they are capable of influencing the structure of the microfilamentous cytoskeleton, which participates in phagocytosis. Two other NAP-1/IL-8-related peptides, platelet factor 4 and connective tissue-activating peptide III, were without effect on expression of CD11b/CD18, CR1, and LAM-1, binding activity of CD11b/CD18, or Fc-mediated phagocytosis, and increased actin polymerization only slightly. Our observations indicate that several members of the NAP-1/IL-8 family of peptides were capable of promoting integrin-mediated adhesion and Fc-mediated phagocytosis, processes important in the recruitment of PMN to sites of inflammation and antimicrobial responses of PMN.
 ...
PMID:Differential effects of neutrophil-activating peptide 1/IL-8 and its homologues on leukocyte adhesion and phagocytosis. 172 41

gamma-Immune protein-10 (gamma-IP10) is a cytokine whose expression has been shown to be induced by interferon-gamma. It is a member of a group of closely related cytokines (e.g., interleukin 8 and platelet factor 4) with chemotactic properties. gamma-IP10 has been detected in keratinocytes, lymphocytes, monocytes, and endothelial cells in immunologically mediated processes, such as positive tuberculin skin tests, and in growth-activated keratinocytes, such as in psoriasis. Keratinocytes in normal epidermis do not produce gamma-IP10. We tested the hypothesis that keratinocytes adjacent to dysplastic nevi and melanomas would produce gamma-IP10, perhaps as part of an immune response to a tumor, and that this response would not be seen in ordinary melanocytic nevi. We used an affinity-purified, polyclonal rabbit anti-gamma-IP10 antibody to examine 10 nevi with moderate to severe histologic dysplasia, one superficial spreading melanoma, and 10 compound melanocytic nevi with no features of dysplasia. As predicted, keratinocytes surrounding all of the cytologically atypical melanocytic lesions displayed strong staining with gamma-IP10. There was no staining of keratinocytes adjacent to ordinary melanocytic nevi. The observed keratinocyte staining with gamma-IP10 may be related to a host immune response to antigenically abnormal cells.
 ...
PMID:Detection of cytokine-induced protein gamma-immune protein-10 (gamma-IP10) in atypical melanocytic proliferations. 172 47

The human melanoma growth-stimulatory activities (MGSA alpha, beta, gamma/GRO) are products of immediate early genes coding for cytokines that exhibit sequence similarity to platelet factor-4 and beta-thromboglobulin. MGSA/GRO alpha has been demonstrated to partially complete for binding to the approximately 58-kDa neutrophil receptor for another beta-thromboglobulin-related chemotactic protein, IL-8. We demonstrate that when [125I]MGSA/GRO alpha was cross-linked to receptors/binding proteins from human placenta, there were two major [125I]MGSA cross-linked bands of approximately 64,000 and approximately 84,000 Mr. Because [125I]MGSA exists primarily in monomer and dimer forms at the concentrations used here, it is not clear whether the receptor/binding proteins represented by the cross-linked bands are approximately 50,000 and approximately 70,000 or approximately 58,000 and approximately 78,000 Mr. Ligand binding to the receptor proteins is associated with enhanced tyrosine phosphorylation of a number of substrates, including proteins in the same Mr range as the MGSA/GRO receptor/binding proteins.
 ...
PMID:The melanoma growth stimulatory activity receptor consists of two proteins. Ligand binding results in enhanced tyrosine phosphorylation. 172 65

The capacity of human melanocytes and melanoma cells to produce IL-8 and monocyte chemotactic and activating factor (MCAF) was investigated. Melanocytes expressed mRNA for IL-8 and MCAF, when stimulated with either IL-1 alpha or TNF alpha, but not when stimulated with IL-6, IFN gamma, or LPS alone. IL-8 and MCAF could be induced in a dose-dependent fashion with doses as low as 0.1 ng/ml TNF alpha and 0.5 ng/ml IL-1 alpha. IL-8 and MCAF mRNA were rapidly expressed and peaked between 2 and 4 h for IL-8 and between 4 and 8 h for MCAF. This correlated well with the accumulation of IL-8 antigen as measured by a radioimmunoassay. Supernatants from melanocyte cultures stimulated with either IL-1 alpha or TNF alpha and separated on a heparin-Sepharose column became positive for neutrophil and monocyte chemotactic activity in a dose- and time-dependent fashion. When IFN gamma was added to melanocyte cultures stimulated with suboptimal doses of TNF alpha there was a synergistic increase in secreted IL-8 protein and monocyte chemotactic activity. These data provide further evidence for the possible role of melanocytes in the initiation of an inflammatory reaction. Three different malignant melanoma cell lines stimulated with either TNF alpha or IL-1 alpha expressed IL-8 mRNA, but not mRNA for MCAF. The IL-8 mRNA signal corresponded well with the amount of secreted IL-8 protein. These data suggest that IL-8 and MCAF may play a role in growth regulation and spreading of melanomas.
 ...
PMID:Expression and secretion of leukocyte chemotactic cytokines by normal human melanocytes and melanoma cells. 187 58

A family consisting of at least ten distinct novel 8-10 kd cytokines has been identified over the past 12 years. These cytokines exhibit from 20 to 45% homology in amino acid sequence, are probably all basic heparin-binding polypeptides, and have proinflammatory and reparative activities. The cDNA for these cytokines are characterized by conserved single open reading frames, typical signal sequences in the 5' region, and AT rich sequences in the 3' untranslated regions. Those human cytokines known as interleukin 8, platelet factor 4, beta thromboglobulin, IP-10 and melanoma growth stimulating factor or GRO can be assigned to a subfamily based on their location on chromosome 4 and unique structural features, whereas the second subset consisting of LD78, ACT-2, I-309, RANTES, and macrophage chemotactic and activating factor (MCAF) are all closely linked on human chromosome 17. In this review we have summarized and discussed the available information concerning the regulation and structure of the genes, the structure and biochemical properties of the polypeptide products, their receptors, signal transduction, cell sources, and in vitro as well as in vivo activities of these cytokines.
 ...
PMID:Properties of the novel proinflammatory supergene "intercrine" cytokine family. 191 Jun 90

Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8, suggested gene symbol IL8) is a cytokine that chemoattracts and activates neutrophils. Using a panel of human-rodent cell hybrids that preferentially segregate human chromosomes and in situ hybridization, the MDNCF/IL-8 gene was placed on the human gene map at position 4q12-q21. This is the same location where at least three other members (platelet factor 4, melanoma growth stimulatory activity, and interferon-gamma induced factor) of the platelet factor 4 gene super-family reside. In addition, a restriction fragment length polymorphism was identified using MDNCF as a probe in screening genomic DNA digested with HindIII from unrelated individuals.
 ...
PMID:Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily. 196 88

Expression of the cytokine gene gro, also known as melanoma growth stimulatory activity, is induced by inflammatory stimuli, including IL-1. To determine whether gro expression is regulated at a post-transcriptional level, the effect of IL-1 on gro mRNA stability was examined. Treatment of fibroblasts with IL-1 beta caused a dose-dependent induction of gro mRNA. When IL-1 was withdrawn, gro mRNA decayed rapidly with a half life of 1 hour. This decay occurred whether or not actinomycin D was added to block new transcription. In contrast, when IL-1 was present in the medium, the level of gro mRNA was stable over 8 hours following addition of actinomycin D. In addition, the stability of a related mRNA, IL-8, was found to be regulated by IL-1. To examine whether Northern results reflected expression of gro alpha, or of the closely related genes, gro beta and gro gamma, RNA samples were analyzed by PCR. All three genes were found to be induced by IL-1 and all mRNAs were stabilized in the presence of IL-1. Northern analysis revealed a minor species of gro mRNA which lacked poly(A). The pattern of expression of this RNA suggested that it was a decay intermediate of one or more of the gro mRNAs. The findings indicate that mRNA stabilization is an important component of IL-1 induced gene expression.
 ...
PMID:Post-transcriptional regulation of gro alpha, beta, gamma, and IL-8 mRNAs by IL-1 beta. 201 72

In order to identify novel mediators synthesized in activated macrophages, a cDNA library was prepared from cultures of the mouse macrophage cell line RAW 264.7 that had been treated with lymphokine-rich conditioned medium from mitogen-stimulated mouse spleen cells. Differential plaque hybridization identified a cDNA, designated m119, that detected a 1.6-kilobase mRNA that accumulated in response to gamma-interferon (IFN-gamma) but not in response to other macrophage activators, including IFN-alpha, IFN-beta, and lipopolysaccharide. The mRNA encoded a predicted protein of Mr 14,461 containing a 21-amino acid signal peptide. The primary structure of the predicted protein indicated that it is a member of a recently described family of cytokines related to platelet factor 4, including Gro/melanoma growth stimulatory activity and neutrophil-activating peptide/interleukin 8. The selective induction of the m119 mRNA by IFN-gamma that the predicted m119 protein mediates a macrophage activity regulated by IFN-gamma. The m119 protein may be a cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory responses. It is proposed that the gene encoding this protein be called mig, for monokine induced by gamma interferon.
 ...
PMID:A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. 211 67


1 2 3 4 5 6 7 8 9 10 Next >>