UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sensitive enzyme-linked immunosorbent assay (ELISA) for rat interleukin 8/cytokine-induced neutrophil chemoattractant (CINC) has been established by using biotin-conjugated anti-CINC rabbit IgG. The biotin-streptavidin sandwich ELISA detected CINC at concentrations from 3 pg/ml up to 30 ng/ml. The concentration of CINC in the pouch fluid (exudate) of rat carrageenin-induced inflammation was measured by the ELISA. After a time lag of about 2 h, neutrophils steadily accumulated in the carrageenin/air-pouch until 8 h. Similarly, the CINC level of exudate increased after about a 2-h lag, and reached a maximum (134 ng/ml) at 8 h, and thereafter decreased to a negligible concentration at 24 h after carrageenin injection. In association with the rise in CINC level, the concentration of exudate 96-kDa gelatinase corresponding to neutrophil gelatinase/type IV collagenase increased with time. The results suggest that CINC contributes, at least in part, to the neutrophil migration into the inflammatory lesion of the carrageenin-induced inflammation in rats.
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PMID:Changes in the levels of rat interleukin 8/CINC and gelatinase in the exudate of carrageenin-induced inflammation in rats. 133 56

Gelatinases (type IV collagenases) produced by normal peripheral blood leukocytes were studied by the use of a substrate conversion assay. When monocytes were stimulated with IL-1 beta discrete amounts of a 85-kDa gelatinase were detected. This type of gelatinase comigrated with a phorbol ester-inducible metalloproteinase from human tumor cells. The levels of induction of the monocytic enzyme after stimulation with IL-1, double-stranded RNA, LPS, and mitogens paralleled those of the secondary cytokine IL-6. When peripheral blood neutrophils were stimulated with IL-8 or PMA significant amounts of a 91-kDa neutrophil gelatinase were released, whereas with IL-1 beta no effect was observed. Both neutrophil and monocyte gelatinases cross-reacted in immunoprecipitation experiments with tumor cell-derived gelatinases. Further evidence for structural similarity between the IL-1-inducible monocytic (85 kDa) and the IL-8-regulated neutrophilic (91 kDa) gelatinases was obtained after purification of the proteins to homogeneity: both gelatinases possessed an identical amino terminal amino acid sequence and appeared as truncated forms of gelatinase from tumor cells. Synovial fluids of arthritic joints contained extremely high concentrations of the 91-kDa gelatinase. The concentrations of this type of gelatinase were correlated with the titers of the marker cytokine IL-6. The controlled production and activity of leukocyte-derived gelatinase may play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. In the arthritis patient this enzyme might contribute to the pathogenesis of joint destruction and might constitute a useful marker of disease status.
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PMID:Cytokine-mediated regulation of human leukocyte gelatinases and role in arthritis. 193 76

UV radiation has been shown to play a role in the initiation of human cutaneous melanoma, but its role in the development of malignant melanoma to the metastatic state is not very well defined. Although previous studies have concentrated on the effect of UV-B on the host immune response, the effect of UV-B on the tumor cells was not elucidated. Here we show that UV-B can induce interleukin 8 (IL-8) mRNA and protein secretion in human cutaneous melanoma with negligible expression of IL-8. UV-B-induced IL-8 was constitutively expressed 60 days after irradiation in tumors implanted in mice. Induction of IL-8 was UV-B dose dependent and blocked by cyclohexamide, indicating that de novo protein synthesis is required for its expression. The UV-irradiated cells demonstrated enhanced tumorigenicity and metastatic potential in nude mice. The increase in tumorigenicity and metastatic ability could be explained by the increase in Mr 72,000 type IV collagenase activity and angiogenesis attributed to the induction of IL-8 after irradiation. The acquisition of the metastatic phenotype induced by UV-B could not be attributed to abnormalities in the p53 or MTS-1 (p16INK4) genes. To the best of our knowledge, this is the first report to show that UV-B can increase the aggressiveness of human cutaneous melanoma for growth and metastasis.
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PMID:Ultraviolet B irradiation promotes tumorigenic and metastatic properties in primary cutaneous melanoma via induction of interleukin 8. 754 20

Stimulated human osteosarcoma cells (MG-63) were used as a source of granulocyte chemotactic protein (GCP). In addition to the previously isolated GCP-1/IL-8, natural forms of GRO alpha, GRO gamma, and IP-10 were purified and identified by amino acid sequence analysis. Further, a novel GCP, GCP-2, was isolated in its natural form (6 kDa) and was found to be structurally related to the other members of the IL-8 family. GRO alpha, IP-10, and GCP-2 showed heterogeneity, in that several forms of each protein were recovered. These differed in truncation at the amino terminus. Reverse phase HPLC allowed us to separate four such different forms of GCP-2. These tumor-derived factors were compared in granulocyte activation and chemotaxis assays. IL-8 induced neutrophil gelatinase B release at 2 nM, but GRO alpha and GCP-2 showed a 5- to 10-fold lower specific activity. When the migration of granulocytes through polycarbonate micropore membranes was measured, GCP-2 and GRO alpha had a maximal chemotactic index comparable to that of IL-8. The minimal effective dose for GCP-2 and GRO alpha was 3 to 10 nM, whereas the specific activity of IL-8 was at least 10-fold higher. IP-10 was not active in this assay at doses up to 100 nM. Finally, in vivo chemotaxis was measured by using granulocyte recruitment in the rabbit skin model. After intradermal injection of 200 ng/site, GCP-2 provoked a significant granulocyte infiltration, albeit to a lesser extent than did IL-8 and GRO alpha. GCP-2 did not attract monocytes in vivo nor did it induce the cells in vitro to migrate or to produce enzyme. In conclusion, this study reveals a new member of the IL-8 family and shows that these related inflammatory mediators possess different potencies and efficacies towards granulocytes.
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PMID:Identification of a novel granulocyte chemotactic protein (GCP-2) from human tumor cells. In vitro and in vivo comparison with natural forms of GRO, IP-10, and IL-8. 842 27

The purpose of this study was to determine whether the expression level of several metastasis-regulating genes correlates with the metastatic potential of human prostate cancer cells implanted into the prostate of nude mice. The steady-state mRNA expression levels for epidermal growth factor receptor (EGFR; growth), basic fibroblast growth factor (bFGF) and interleukin (IL)-8 (angiogenesis), 72-kd and 92-kd type IV collagenase (invasion), E-cadherin (adhesion), and multidrug resistance (mdr-1; drug resistance) were measured by Northern blot and colorimetric in situ hybridization techniques in human PC-3M cells and selected cell variants with different metastatic potentials. Highly metastatic cells growing in culture constitutively and uniformly expressed higher levels of bFGF, IL-8, type IV collagenase, and mdr-1 mRNA transcripts than parental PC-3M cells or low metastatic cells, which displayed a heterogeneous pattern of gene expression. Human prostate cancer cells implanted in nude mice at an ectopic site (subcutaneous) expressed lower levels of EGFR, mdr-1, bFGF, IL-8, and collagenase type IV than those implanted in an orthotopic site (prostate), indicating that the expression of these genes was dependent on the organ environment. Highly metastatic cells growing in the prostate expressed higher levels of EGFR, bFGF, type IV collagenase, and mdr-1 mRNA than low metastatic parental cells in the same site. These data demonstrate a direct correlation between the expression of several metastasis-related genes and the metastatic potential of human prostate cancer cells in nude mice and suggest that multiparametric in situ hybridization analyses can be used to identify the metastatic potential of individual patients' prostate cancers.
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PMID:Correlation of metastasis-related gene expression with metastatic potential in human prostate carcinoma cells implanted in nude mice using an in situ messenger RNA hybridization technique. 913 84

We examined the expression level of several genes that regulate distinct steps of metastasis in formalin-fixed, paraffin-embedded, archival specimens of primary human pancreatic carcinomas from patients undergoing curative surgery. The expression of epidermal growth factor receptor, E-cadherin, type IV collagenase [matrix metalloproteinase (MMP) 2 and MMP-9), basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and interleukin 8 was examined by a colorimetric in situ mRNA hybridization technique. Down-regulation of E-cadherin and up-regulation of type IV collagenase (MMP-9 and MMP-2) at the periphery of the neoplasms (P = 0.0167, 0.0102, and 0.0349, respectively) had significant prognostic value. The ratio of type IV collagenase expression (mean of the expression of MMP-2 and MMP-9) to E-cadherin expression (MMP:E-cadherin ratio) at the periphery of the tumors was significantly higher in patients with recurrent disease (4.7 +/- 2.1) than in patients who were disease free (2.3 +/- 1.7; P = 0.0008). Death from pancreatic cancer was significantly associated with a high MMP:E-cadherin ratio (>3.0) by overall survival analysis (P < 0.0002), whereas a low MMP:E-cadherin ratio (<3.0) was found in seven of eight patients alive 28-64 months after surgery. Multivariate analysis of overall survival showed that the MMP:E-cadherin ratio was a significant independent prognostic factor, whereas stage, nodal metastasis, and histological type were not. These data show that multiparametric analysis for several metastasis-related genes may allow physicians to assess the metastatic potential and hence predict the clinical outcome of individual patients with resectable pancreatic carcinoma.
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PMID:Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma. 991 99

Because routine histopathological examination of primary non-small cell lung cancer does not predict disease outcome, we correlated disease outcome with the expression level of multiple genes that regulate distinct steps of the metastatic process in 60 formalin-fixed, paraffin-embedded, archival specimens of stage I lung carcinoma from patients undergoing curative surgery at the M. D. Anderson Cancer Center. The expression of E-cadherin (related to cell cohesion), type IV collagenase [matrix metalloproteinase (MMP)-2 and MMP-9, related to invasion], and three angiogenic molecules, basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and interleukin 8, were examined by a colorimetric in situ mRNA hybridization technique. The expression levels of the individual genes analyzed by a Cox univariate analysis were not prognostic. In contrast, the ratio between expression of type IV collagenases (mean of the expression of MMP-2 and MMP-9) and E-cadherin, the MMP:E-cadherin ratio (measured at the periphery of each tumor), was significantly higher in patients with recurrent disease than in patients who remained disease free (P = 0.00003). Longer overall survival and reduced disease recurrence rates were significantly associated with a lower MMP:E-cadherin ratio (<2) by a Kaplan-Meier survival analysis (P = 0.0002 and P = 0.0001, respectively). Multiple covariate analyses of overall and disease-free survival also concluded that the MMP:E-cadherin ratio was a significant prognostic factor when corrected for age (P = 0.0001). Determination of this gene expression ratio in individual human lung cancers might therefore be used to direct tailored treatment for individual patients with resectable lung cancer.
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PMID:Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma. 1074 98

The expression of interleukin 8 (IL-8) by human gastric carcinomas directly correlates with tumor vascularity and disease progression. To determine whether IL-8 can act in an autocrine manner to regulate the expression of other disease-progression genes, we examined the expression of IL-8 receptors IL-8RA (CXCR1) and IL-8RB (CXCR2) in six different human gastric carcinoma cell lines and 38 surgical specimens of human gastric carcinomas. All of the gastric carcinoma cell lines expressed mRNA and protein for IL-8RA and IL-8RB protein. In all surgical specimens, the majority of the tumor cells and small vessel endothelial cells stained positive for IL-8RA and IL-8RB protein. In vitro treatment of human gastric cancer MKN-1 cells with exogenous IL-8 enhanced the expression of epidermal growth factor receptor, type IV collagenase (metalloproteinase-9), vascular endothelial growth factor, and IL-8 mRNA. In contrast, treatment with exogenous IL-8 decreased expression of E-cadherin mRNA. IL-8 treatment increased invasive capacity of MKN-1 cells, which was associated with activity of metalloproteinase-9. Collectively, these results demonstrate that human gastric carcinoma cells express receptors for IL-8 and that IL-8 may play a role in the progressive growth of human gastric carcinoma by autocrine/paracrine mechanisms.
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PMID:Regulation of disease-progression genes in human gastric carcinoma cells by interleukin 8. 1091 18

Chemokines are mediators in inflammatory and autoimmune disorders. Aminoterminal truncation of chemokines results in altered specific activities and receptor recognition patterns. Truncated forms of the CXC chemokine interleukin (IL)-8 are more active than full-length IL-8 (1-77), provided the Glu-Leu-Arg (ELR) motif remains intact. Here, a positive feedback loop is demonstrated between gelatinase B, a major secreted matrix metalloproteinase (MMP-9) from neutrophils, and IL-8, the prototype chemokine active on neutrophils. Natural human neutrophil progelatinase B was purified to homogeneity and activated by stromelysin-1. Gelatinase B truncated IL-8(1-77) into IL-8(7-77), resulting in a 10- to 27-fold higher potency in neutrophil activation, as measured by the increase in intracellular Ca(++) concentration, secretion of gelatinase B, and neutrophil chemotaxis. This potentiation correlated with enhanced binding to neutrophils and increased signaling through CXC chemokine receptor-1 (CXCR1), but it was significantly less pronounced on a CXCR2-expressing cell line. Three other CXC chemokines-connective tissue-activating peptide-III (CTAP-III), platelet factor-4 (PF-4), and GRO-alpha-were degraded by gelatinase B. In contrast, the CC chemokines RANTES and monocyte chemotactic protein-2 (MCP-2) were not digested by this enzyme. The observation of differing effects of neutrophil gelatinase B on the proteolysis of IL-8 versus other CXC chemokines and on CXC receptor usage by processed IL-8 yielded insights into the relative activities of chemokines. This led to a better understanding of regulator (IL-8) and effector molecules (gelatinase B) of neutrophils and of mechanisms underlying leukocytosis, shock syndromes, and stem cell mobilization by IL-8. (Blood. 2000;96:2673-2681)
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PMID:Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact. 1102 97

Gelatinase B is a matrix metalloproteinase (MMP-9) expressed under strict control by many cell types including neutrophils, monocytes, macrophages, and tumor cells. MMP-9 is a key mediator in the physiological maintenance of the extracellular matrix both in tissue remodeling and development, while uncontrolled enzyme activity contributes to pathologies such as cancer and inflammation. Neutrophils release MMP-9 from granules in response to IL-8 stimulation. Human MMP-9 has three potential N-linked glycosylation sites and contains a Ser/Pro/Thr rich domain, known as the type V collagen-like domain, which is expected to be heavily O-glycosylated. Indeed, approximately 85% of the total sugars on human neutrophil MMP-9 are O-linked. This paper presents the detailed analysis of picomole amounts of these O-glycans using a novel HPLC-based strategy for O-glycan analysis that provides linkage and arm specific information in addition to monosaccharide sequence. The initial structural assignments were confirmed using HPLC with online MS/MS fragmentation analysis. Twelve sugars were identified that contained from two to nine monosaccharide residues. Most of these contained type 2 core structures with Galbeta1-4GlcNAc (N-acetyl lactosamine) extensions, with or without sialic acid or fucose. The O-glycans were modeled using the oligosaccharide structural database. On the basis of the structure of gelatinase A (MMP-2), a model of MMP-9 suggests that the type V collagen-like domain in gelatinase B is located on a loop remote from the active site. Fourteen potential O-glycosylation sites are multiply presented on this loop of 52 amino acids. Many of the O-glycans identified contain terminal galactose residues that may provide recognition epitopes. Importantly, heavy glycosylation of this loop region, absent in gelatinase A, has considerable implications for the domain organization of MMP-9.
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PMID:O-glycan analysis of natural human neutrophil gelatinase B using a combination of normal phase-HPLC and online tandem mass spectrometry: implications for the domain organization of the enzyme. 1112 94

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