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 identified, by differential cDNA library screening, 15 serum inducible genes in the human diploid fibroblast cell line WI-38. The genes fall into two classes that are distinguished by their dependence on protein synthesis for the induction by serum, i.e., primary and secondary genes. While 11 of these genes encode known proteins, 4 other genes have not been described to date. The former genes encode proteins of diverse functions, including the monocyte-derived neutrophil chemotactic factor (MONAP), calmodulin, tropomyosin, tenascin, collagenase, plasminogen activator inhibitor-2a, the 'sperm-specific' cleavage signal-1 protein, metallothionein IIa and the mitochondrial chaperonin hsp-60. Interestingly, one of the unknown genes contains a large open reading frame for a polypeptide that is highly homologous to a previously unidentified long open reading frame in the opposite strand of the gene coding for the transcription factor HTF-4. We also studied the regulation of these serum-induced genes during cell cycle progression in normally cycling WI-38 and HL-60 cells separated by counterflow elutriation as well as in serum-stimulated HL-60 cells. Our results clearly show that, in contrast to the prevailing opinion, the expression of most genes induced after mitogen stimulation is not subject to a significant regulation in normally proliferating cells. This supports the hypothesis that the progression into S from either G0 or G1 are distinct processes with specific patterns of gene expression.
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PMID:Identification of serum-inducible genes: different patterns of gene regulation during G0-->S and G1-->S progression. 800 57

As part of a program of work to understand the interaction of bacterial chaperonins with human leukocytes, we have examined 2 of the 3 chaperonin 60 (Cpn 60) gene products of the nonpathogenic plant symbiotic bacterium, Rhizobium leguminosarum, for their capacity to induce the production of pro- and antiinflammatory cytokines by human cells. Recombinant R. leguminosarum Cpn 60.1 and 60.3 proteins were added to human monocytes at a range of concentrations, and cytokine production was measured by sandwich enzyme-linked immunosorbent assay. In spite of the fact that the 2 R. leguminosarum Cpn 60 proteins share 74.5% amino acid sequence identity, it was found that Cpn 60.3 induced the production of interleukin (IL)-1beta, tumor necrosis factor alpha, IL-6, IL-8, IL-10, and IL-12, but not IL-4, interferon gamma, or GM-CSF (granulocyte-macrophage colony-stimulating factor), whereas the Cpn 60.1 protein failed to demonstrate any cytokine-inducing activity. The use of neutralizing monoclonal antibodies showed that the cytokine-inducing activity of Cpn 60.3 was dependent on its interaction with CD14. This demonstrates that CD14 mediates not only lipopolysaccharide but also R. leguminosarum Cpn 60.3 cell signaling in human monocytes.
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PMID:Rhizobium leguminosarum chaperonin 60.3, but not chaperonin 60.1, induces cytokine production by human monocytes: activity is dependent on interaction with cell surface CD14. 1238 Jun 80

Tuberculosis is a chronic inflammatory and destructive disease caused by infection with Mycobacterium tuberculosis. We have previously shown that the mycobacterial chaperonin (Cpn)60.1 and 60.2 proteins stimulate human monocytes to secrete pro-inflammatory cytokines. Identification of the cellular mechanisms that contribute to the chronic inflammation characterised by myobacterial infection is therefore of potential therapeutic benefit. In the present study we have investigated the role of the extracellular signal-regulated (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) families in Cpn60-induced cytokine synthesis, and have compared the effects of the bacterial proteins with those of lipopolysaccharide (LPS). Exposure to Cpn60.1, Cpn60.2 or LPS enhanced ERK1/2 activation with increases in phosphorylation evident between 10 and 30 min and maximal after 60-90 min stimulation. Phosphorylation of ERK1/2 in Cpn60-stimulated monocytes was maintained whereas ERK1/2 was rapidly dephosphorylated in LPS-stimulated cells. Exposure to the chaperonins also caused rapid activation of p38(mapk) with kinetics of phosphorylation comparable to those observed in response to LPS. Selective inhibitors of p38(mapk) (SB203580) or of MEK1/2, the direct upstream activator of ERK1/2 (PD98059), reduced the synthesis of IL-1beta, TNFalpha, IL-6 and IL-8 induced by either the chaperonins or LPS. Experiments in which cells were exposed to a combination of both inhibitors led to a nearly complete abrogation of agonist-induced cytokine synthesis. These results show that the p38(mapk) and ERK1/2 signalling pathways are important regulators of the cellular response to mycobacterial chaperonins and that these pathways cooperate to regulate pro-inflammatory cytokine production by human monocytes.
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PMID:Highly homologous Mycobacterium tuberculosis chaperonin 60 proteins with differential CD14 dependencies stimulate cytokine production by human monocytes through cooperative activation of p38 and ERK1/2 mitogen-activated protein kinases. 1717 91

HSP60 has been implicated in chronic inflammatory disease pathogenesis, including chronic obstructive pulmonary disease (COPD), but the mechanisms by which this chaperonin would act are poorly understood. A number of studies suggest a role for extracellular HSP60, since it can be secreted from cells and bind Toll-like receptors; however, the effects of this stimulation have never been extensively studied. We investigated the effects (pro- or anti-inflammatory) of HSP60 in human bronchial epithelial cells (16-HBE) alone and in comparison with oxidative, inflammatory, or bacterial challenges. 16-HBE cells were cultured for 1-4 h in the absence or presence of HSP60, H2O2, lipopolysaccharide (LPS), or cytomix. The cell response was evaluated by measuring the expression of IL-8 and IL-10, respectively, pro- and anti-inflammatory cytokines involved in COPD pathogenesis, as well as of pertinent TLR-4 pathway mediators. Stimulation with HSP60 up-regulated IL-8 at mRNA and protein levels and down-regulated IL-10 mRNA and protein. Likewise, CREB1 mRNA was up-regulated. H2O2 and LPS up-regulated IL-8. Experiments with an inhibitor for p38 showed that this mitogen-activated protein kinase could be involved in the HSP60-mediated pro-inflammatory effects. HSP60 showed pro-inflammatory properties in bronchial epithelial cells mediated by activation of TLR-4-related molecules. The results should prompt further studies on more complex ex-vivo or in-vivo models with the aim to elucidate further the role of those molecules in the pathogenesis of COPD.
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PMID:HSP60 activity on human bronchial epithelial cells. 2897 40