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)

Local production of cytokines plays a critical role in the regulation of pathophysiologic processes leading to rejection of transplanted organs. In the present study, the possible role of interleukin-17 (IL-17), a recently identified cytokine with unique properties, was investigated. IL-17 is specifically produced by activated T cells, whereas biological activities are restricted to the activation of nonhematopoietic cells. In vitro, IL-17 induced primary human proximal tubular epithelial cells, a type of cell regulating local interstitial inflammatory responses, to secrete higher levels of IL-6, IL-8, and monocyte chemoattractant protein-1, but not of the chemokine RANTES. The effect was specific for IL-17, because it was completely abrogated by a neutralizing anti-IL-17 antibody and was demonstrated to be dose- and time-dependent. In addition, IL-17 increased the production of complement component C3 by human proximal tubular epithelial cells, but not of other complement components. Immunofluorescence showed expression of IL-17 in kidney biopsies from patients suffering from graft rejection (8 of 8 positive), whereas pretransplant biopsies and normal kidneys were negative (0 of 6). Analysis of whole kidney isolates confirmed the presence of IL-17 mRNA by reverse transcription-PCR. IL-17 expression could also be found in in vitro cultured and activated graft-infiltrating T cells. These results represent the first demonstration of IL-17 protein expression in pathologic conditions and suggest that IL-17 might be important in the regulation of local inflammatory responses.
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PMID:Interleukin-17 activates human renal epithelial cells in vitro and is expressed during renal allograft rejection. 969 77

Interleukin-17 (IL-17) has been characterized as a proinflammatory cytokine produced by CD4+ activated memory T cells. In an effort to elucidate the biological effects of IL-17 in glial cells, we investigated the ability of this cytokine in order to activate nuclear factor (NF)-kappaB, which is being discussed as one of the most important transcription factors in the regulation of neuronal and glial cell function. Activation of NF-kappaB involves the degradation of its cytoplasmatic inhibitor IkappaB-alpha, which allows the nuclear translocation of NF-kappaB, and ensures transcriptional activation of genes including IkappaB-alpha itself. Using a competitive RT-PCR, we examined the IL-17-induced IkappaB-alpha mRNA expression in glioblastoma cells, and we examined IL-17 up-regulated IkappaB-alpha mRNA expression in a dose- and time-dependent fashion with a maximum time between 1 and 3 h. This induction could be inhibited by Calphostin C (protein kinase C inhibitor) and genistein (tyrosine kinase inhibitor). After 60 min of IL-17 stimulation, a degradation of the IkappaB-alpha protein was detectable. Furthermore, IL-17 stimulated the secretion of IL-6 and IL-8 in glial cells, and IL-17 and IL-1beta in combination showed a superadditive effect. We suggest IL-17 to play a role as an immune factor, possibly involved in complex pathophysiological interactions of neurodegenerative diseases.
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PMID:Interleukin-17 stimulates the expression of IkappaB alpha mRNA and the secretion of IL-6 and IL-8 in glioblastoma cell lines. 1058 Aug 7

Interleukin-17 (IL-17) has been characterized as a proinflammatory cytokine produced by CD4+ CD45RO+ memory T cells. Overproduction of IL-17 was detected in the synovium of patients with rheumatoid arthritis (RA) compared to patients with osteoarthritis. In contrast to the restricted expression of IL-17, the IL-17 receptor (IL-17R/CDw217) is expressed ubiquitously. Using a real-time RT-PCR assay, we detected similar absolute levels of IL-17R mRNA expression in fibroblast-like synoviocytes (SFC) from patients with RA (mean 9 pg/microg total RNA; ranged from 0.1 pg to 96 pg IL-17R mRNA/microg total RNA) compared to synoviocytes of non-RA patients. Analysis of the IL-17R surface expression confirmed the results obtained for IL-17R mRNA expression. Exposure of SFC to IL-17 led to a mRNA induction of CXC chemokines IL-8, GRO-alpha and GRO-beta. An anti-IL-17 antibody blocked these effects of IL-17. The MAPK p38 appears necessary for the regulation of IL-8, GRO-alpha and GRO-beta expression as shown by inhibition with SB203580. The inhibitors genistein (tyrosine kinase inhibitor) and calphostin C (inhibitor of protein kinase C) reduced significantly the IL-17-stimulated mRNA expression of IL-8, GRO-alpha and GRO-beta in SFC, whereas PD98059 (inhibitor of MEK-1/2) was without effect. Pharmacological drugs used in therapy of RA, such as cyclosporin and methotrexate, induced a fourfold increase of IL-17R mRNA expression and augmented the IL-17-stimulated IL-8 expression. Our results support the hypothesis that IL-17/IL-17R may play a significant role in the pathogenesis of RA contributing to an unbalanced production of cytokines as well as participating in connective tissue remodelling.
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PMID:Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of patients with rheumatoid arthritis. 1196 73

Interleukin-17 (IL-17) is a T cell derived pro-inflammatory cytokine exhibiting multiple biological activities in a variety of cells. In our previous study, we found that IL-17 expressed early on borderline change of renal allograft rejection by Banff classification both in rat renal allograft model and human renal specimens. Renal epithelial cells (RECs) are the important targets in renal allograft rejection. The purpose of this study was to explore the signalling pathways by which human interleukin-17 (hIL-17) contributes to renal allograft rejection by inducing IL-6, IL-8 and MCP-1 expression in human renal epithelial cells (hRECs). Using reverse transcriptase-polymerase chain reaction (RT-PCR), immunoprecipitation and western blot analysis, we report that the early signalling events triggered by the hIL-17 involved tyrosyl phosphorylation of proteins and increased the levels of IL-6, IL-8 and MCP-1 in a dose-dependent manner. Tyrosyl phosphorylation of proteins was induced by IL-17 in 1 min and peaked in 5 min. Further, IL-17 induced the phosphorylation of src kinase and mitogen-activated protein (MAP) kinase. Using a specific src kinase inhibitor, PP2, to treat the hRECs before hIL-17 stimulation, we found that PP2 not only inhibited the phosphorylation of src kinase but also inhibited IL-6, IL-8 and MCP-1 mRNA expression, in a dose-dependent manner. These findings provide the first evidence that the mechanism of IL-17 signalling involves src/MAPK cascades activation.
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PMID:Interleukin-17 induces src/MAPK cascades activation in human renal epithelial cells. 1229 9

Interleukin-17 (IL-17) is a recently cloned cytokine secreted by activated memory CD4(+) T cells and modulates the early stage of immune responses. IL-17 stimulates epithelial, endothelial and fibroblastic stromal cells to secrete several cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, as well as prostoglandin E2. IL-17 also stimulates the production and expression of proinflammatory cytokines, IL-1beta and tumor necrosis factor-alpha by human macrophages. IL-17 may be involved in osteoclastic bone resorption in rheumatoid arthritis patients. Recently, several groups have reported that IL-17 plays important roles in both the immune response and joint destruction in patients with rheumatoid arthritis. The control of IL-17 expression in these patients could provide directions for the development of new treatment strategies for joint destruction. (c) 2002 Prous Science. All rights reserved.
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PMID:The Role of IL-17 in Joint Destruction. 1267 40

Interleukin-17 (IL-17) has been characterized as a proinflammatory cytokine produced by CD4+ CD45RO+ memory T cells. Overproduction of IL-17 was detected in the synovium of patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis. This study examines differentially expressed genes after the stimulation of fibroblast-like synoviocytes of RA patients by IL-17. Among these genes we identified the following: tumor necrosis factor-stimulated gene-6 (TSG-6), IL-6, IL-8, GRO-beta, and bone morphogenetic protein-6 with an expression 3.6-10.6-fold that in the unstimulated control. IL-17 augmented the expression of TSG-6, a hyaluronan-binding protein, in a time- and dose-dependent manner. IL-17 showed additive effects with IL-1beta and tumour necrosis factor-alpha on the expression of TSG-6, IL-6 and IL-8. The mitogen-activated protein kinase p38 seems to be necessary for the regulation of TSG-6 expression by IL-17, as shown by inhibition with SB203580. Our results support the hypothesis that IL-17 is important in the pathogenesis of RA, contributing to an unbalanced production of cytokines as well as participating in connective tissue remodeling.
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PMID:Gene expression induced by interleukin-17 in fibroblast-like synoviocytes of patients with rheumatoid arthritis: upregulation of hyaluronan-binding protein TSG-6. 1282 53

Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4+ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3+ CD4+ CD45RO+, a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth.
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PMID:Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and Sezary syndrome). 1530 82

Interleukin-17 (IL-17), initially reported as CTLA-8, is a proinflammatory cytokine produced mainly by activated T cells. In the present study, the cDNA of a swine IL-17 (PoIL-17) gene was cloned from activated neonatal thymocytes, and the recombinant PoIL-17 (rPoIL-17) was biologically characterized. The complete open reading frame (ORF) of PoIL-17 contains 462-bp coding deduced 153 amino acid residues, with a calculated molecular weight of 17.3 kDa. The amino acid sequence showed 72.9%, 64.9%, 64.7%, 60.1%, and 47.4% similarities with that of human, rat, mouse, Herpesvirus saimiri ORF 13, and chicken, respectively. The six cysteine residues conserved over species including the virus were observed in PoIL-17. We successfully prepared the recombinant mature form of PoIL-17 and analyzed its biologic activities for swine splenocytes. RT-PCR analysis revealed a marked upregulation of expression of IL-1beta, IL-8, tumor necrosis factor-alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1 (MCP-1) mRNA expression in splenocytes treated with 100 ng/ml rPoIL-17 for 3 h. Furthermore, a swine chemokine, alveolar macrophage-derived neutrophil chemotactic factor II (AMCF-II), which was classified into the CXC subfamily was also augmented in mRNA level. This evidence indicates that recombinat PoIL-17 expressed in Escherichia coli was biologically active and exerted similar effects to those of a human (HuIL-17) and murine IL-17 (MuIL-17). The PoIL-17 mRNA is strongly expressed in the adult heart, skin, and, interestingly, intestinal tissues, including mesenteric lymph nodes but is restricted in neonatal tissues by using real-time quantitative RT-PCR. The gene sequence and biologically active recombinat protein for PoIL-17 will be useful for elucidation of the role of IL-17 in the regulation of intestinal immune responses.
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PMID:Cloning and characterization of Swine interleukin-17, preferentially expressed in the intestines. 1545 Jan 31

Interleukin-17 (IL-17) is a CD4 T cell-derived proinflammatry and proangiogenic cytokine. In this study, we investigated the effects of this cytokine on vascular endothelial cell growth induced by a well-known direct angiogenic factor bFGF, HGF, VEGF, CXCL5/ENA-78 or CXCL8/IL-8. While a wide range of doses of IL-17 alone did not show the ability to stimulate the growth of human dermal microvascular endothelial cells (HMVECs), bFGF, HGF, VEGF, CXCL5 or CXCL8 significantly induced the growth of HMVECs in vitro. When bFGF and IL-17 were used in combination, 10 or 100 ng/ml IL-17 enhanced 10 ng/ml bFGF-induced growth of HMVECs. Similarly, when HGF and IL-17 were combined together, 10 or 100 ng/ml IL-17 potentiated 10 ng/ml HGF-induced growth of HMVECs. When VEGF and IL-17 were used together, 10 ng/ml IL-17 did not significantly enhance 10 ng/ml VEGF-induced growth, whereas 100 ng/ml IL-17 clearly promoted 10ng/ml VEGF-mediated proliferation of HMVECs. On the contrary, IL-17 did not augment CXCL5- and CXCL8-mediated growth. These results indicate that IL-17 itself does not have the capability to stimulate the growth of vascular endothelial cells, whereas IL-17 is able to selectively enhance the mitogenic activity of bFGF, HGF, and VEGF for vascular endothelial cells. Our findings also suggest that IL-17 may promote bFGF-, HGF- and VEGF-mediated angiogenesis through enhancing bFGF-, HGF- and VEGF-induced growth of vascular endothelial cells.
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PMID:Interleukin-17 enhances bFGF-, HGF- and VEGF-induced growth of vascular endothelial cells. 1586 Feb 17

Interleukin-17 (IL-17) is a proinflammatory cytokine produced by activated memory T cells, and it appears to play an upstream role in T cell-triggered inflammation by stimulating stromal cells to secrete other cytokines. We hypothesize that IL-17 plays a role in the recruitment of neutrophils in the bovine mammary gland during infection or immune-mediated inflammation. The rapid amplification of cDNA ends (RACE) method was used to obtain a cDNA of bovine IL-17 (BoIL-17) containing a 462-bp open reading frame (ORF) encoding a protein of 153 amino acids (aa) with a molecular mass of 17.2 kDa, a 23-residue NH(2)-terminal signal peptide, a single potential N-linked glycosylation site, and 6 cysteine residues. BoIL-17 protein shared 73.5% identity with the human protein and 67% with the mouse and rat proteins. Sf9 insect cells were transfected with BoIL-17 cDNA, and supernatant was tested for biologic activity on a primary culture of bovine mammary epithelial cells (MECs). mRNA synthesis of IL-6, IL-8, and growth-related oncogene alpha (Groalpha) was induced, suggesting a functional role for IL-17 in mammary immunity.
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PMID:Determination and characterization of bovine interleukin-17 cDNA. 1654 36


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