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)

The seminal plasma levels of soluble Fas (sFas) and interleukins IL-6 and IL-8 were measured and their relationship with semen qualities was examined. The seminal plasma sFas level in fertile males was significantly higher than that in the infertile group. On the other hand, seminal plasma level of IL-6 was significantly lower in fertile males than in the infertile group. In the infertile group, patients with oligozoospermia had a lower seminal plasma sFas and a higher IL-6 level than those with normal sperm concentration. There was an inverse correlation between IL-6 and sperm concentration in infertile patients. Seminal plasma IL-8 was not correlated with sperm parameters. It would appear that certain kinds of cytokine in the seminal plasma might play an important role in improving semen quality.
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PMID:Soluble Fas and interleukin-6 and interleukin-8 levels in seminal plasma of infertile men. 1455 27

Interleukin (IL)-18 is a novel cytokine expressing at inflammatory lesion. In this study, to evaluate the clinical significance of IL-18 determination, we have examined serum IL-18, inflammation markers, sFas, and sFas-ligand concentrations in patients with rheumatoid arthritis(RA). Serum was obtained from 56 RA patients aged 35-74 years, 16 osteoarthritis (OA) patients aged 36-78 years and 178 healthy subjects aged 20-72 years and IL-18 was measured by ELISA. Serum IL-18 concentrations in RA (240.1 +/- 15.6 pg/ml, mean +/- SE) were significantly higher than OA (151.8 +/- 12.7 pg/ml, p < 0.005) and healthy controls(141.5 +/- 26.1 pg/ml, p < 0.001). Serum IL-18 levels were significantly increased in II to IV stages of RA (stage II; 218.6 +/- 31.2 pg/ml, stage III; 258.7 +/- 38.4 pg/ml, stage IV; 231.6 +/- 13.1 pg/ml) than those in OA. Furthermore, a positive correlation was observed between serum IL-18 concentration and serum Fas level in patients with RA (r = 0.472), whereas there was no significant correlation between serum IL-18 and sFas-ligand or other inflammatory markers (CRP, RF, CA-RF, IL-6, and IL-8). The present study showed that serum IL-18 level increased in RA, but it is unknown how IL-18 is involved in the pathogenesis of RA. Further study will be necessary to clarify the role of IL-18 in RA.
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PMID:[Clinical significance of serum IL-18 determination in rheumatoid arthritis]. 1502 13

The balance between polymorphonuclear leukocytes (PMNL) apoptosis and necrosis in inflamed tissues is an important determinant of the degree of tissue injury. To prevent senescent PMNL from releasing their toxic contents into surrounding tissues, these cells become apoptotic and are then internalized by tissue macrophages. PMNL apoptosis and subsequent ingestion by macrophages are the major mechanisms for clearing PMNL that have been recruited to the inflamed sites and thus for promoting resolution of the inflammation. PMNL have a short half-life that is extended at the inflamed site by pro-inflammatory cytokines including Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Interleukin-8 (IL-8), Gro-alpha, and they contact with the bacterial cell walls containing lipopolysaccharides (LPS). Conversely, anti-inflammatory cytokines, such as IL-10, accelerate the apoptosis of LPS-activated PMNL. Spontaneous PMNL apoptosis does not require Fas ligation but involves proteolytic cascades -caspases (particularly caspases 3 and 8), calpains and the proteasome-that activate kinases, e.g. caspase 3-mediated activation of protein kinase C-delta, dissociate actin-binding proteins from filamentous actin, and participate in cell surface as well as nuclear morphological transformations. Members of the Bcl-2 protein family, Mcl-1 and A1, are involved in the regulation of PMNL apoptosis. Cell surface receptors and protein kinases, particularly mitogen-activated protein kinases (MAPK), also play critical roles in transducing the signals that result in PMNL apoptosis or extended survival. A growing understanding of the mechanisms regulating leukocyte apoptosis and of the molecules mediating safe phagocytic clearance of dying cells may yield new insights into the pathogenesis of inflammatory diseases. In this regard, therapeutic strategies to resolve chronic inflammation could usefully target PMNL. This review summarises current knowledge on the molecular mechanisms and components of PMNL apoptosis.
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PMID:Molecular regulation of neutrophil apoptosis and potential targets for therapeutic strategy against the inflammatory process. 1503 37

Correlations between local expression of insulin-like growth factor 1, insulin-like growth factor receptor, epithelial growth factor, transforming growth beta2 factor, PCNA, TNF-alpha, TNF receptor 1, Fas, FasL, IFN-gamma, IL-1beta, IL-4, IL-6, IL-8, IL-10, and IL-12 genes in intact and hyperplastic endometrium and in the endometrium after hormone therapy were analyzed. Numerous correlations at the proliferation and secretion stages of the menstrual cycle indicate balanced cytokine system. The number of correlations decreases in glandular cystic and more so in atypical hyperplasia, indicating imbalance in the cytokine system. Dufastone and zoladex therapy did not lead to recovery of this balance, but higher correlations between the expression of some factors of cell proliferation attest to the beginning of normalization of pathologically changed endometrium.
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PMID:Correlations in the cytokine system in endometrial hyperplasia. 1509 42

There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL) that are used by researchers worldwide. Detailed data about their differentiation status and genetic alterations are present in the literature, but a systematic correlation with cell biological behavior is often lacking. PDCL ( n=12) were clustered by source of tumor cell (ascites, primary tumor, metastasis), and the data of functional cell biology were correlated with the reported structural and genetic profiles. Major histocompatibility complex expression, chemosensitivity and aneuploidia appeared to be related to the source of PDCL, and proliferative capacity appeared to be related to the grade of differentiation. No correlation between genetic/structural features of PDCL and biological behavior was found. All the cell lines appeared generally insensitive to in vitro treatment with 5-fluorouracil and showed variable degrees of susceptibility to gemcitabine, raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated apoptosis but were significantly sensitive to the pro-apoptotic effect of inflammatory cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)alpha and interferon gamma]. PDCL were characterized for the secretion of several factors relevant to the tumor-immune cross talk. Vascular endothelial growth factor, CCL2, CCL5 and transforming growth factor beta were the factors most frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1beta and TNFalpha were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a "morphological" classification for the in vitro studies of pancreatic cancer.
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PMID:A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile. 1525 55

Fas (APO-1/CD95) is the prototypic death receptor, and the molecular mechanisms of Fas-induced apoptosis are comparably well understood. Here, we show that Fas activates NFkappaB via a pathway involving RIP, FADD, and caspase-8. Remarkably, the enzymatic activity of the latter was dispensable for Fas-induced NFkappaB signaling pointing to a scaffolding-related function of caspase-8 in nonapoptotic Fas signaling. NFkappaB was activated by overexpressed FLIPL and FLIPS in a cell type-specific manner. However, in the context of Fas signaling both isoforms blocked FasL-induced NFkappaB activation. Moreover, down-regulation of both endogenous FLIP isoforms or of endogenous FLIPL alone was sufficient to enhance FasL-induced expression of the NFkappaB target gene IL8. As NFkappaB signaling is inhibited during apoptosis, FasL-induced NFkappaB activation was most prominent in cells that were protected by Bcl2 expression or caspase inhibitors and expressed no or minute amounts of FLIP. Thus, protection against Fas-induced apoptosis in a FLIP-independent manner converted a proapoptotic Fas signal into an inflammatory NFkappaB-related response.
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PMID:NFkappaB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIP. 1528 96

Fas ligand (FasL) has been well characterized as a death factor. However, recent studies revealed that FasL possesses inflammatory activity. Here we found that FasL induces production of the inflammatory chemokine IL-8 without inducing apoptosis in HEK293 cells. Reporter gene assays involving wild-type and mutated IL-8 promoters and NF-kappaB- and AP-1 reporter constructs indicated that an FasL-induced NF-kappaB and AP-1 activity are required for maximal promoter activity. FasL induced NF-kappaB activation with slower kinetics than did TNF-alpha, yet this response was cell autonomous and not mediated by secondary paracrine factors. The death domain of Fas, FADD, and caspase-8 were required for NF-kappaB activation by FasL. A dominant-negative mutant of IKKgamma inhibited the FasL-induced NF-kappaB activation. However, TRADD and RIP, which are essential for the TNF-alpha-induced NF-kappaB activation, were not involved in the FasL-induced NF-kappaB activation. Moreover, CLARP/FLIP inhibited the FasL- but not the TNF-alpha-induced NF-kappaB activation. These results show that FasL induces NF-kappaB activation and IL-8 production by a novel mechanism, distinct from that of TNF-alpha. In addition, we found that mouse FADD had a dominant-negative effect on the FasL-induced NF-kappaB activation in HEK293 cells, which may indicate a species difference between human and mouse in the FasL-induced NF-kappaB activation.
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PMID:Fas ligand induces cell-autonomous NF-kappaB activation and interleukin-8 production by a mechanism distinct from that of tumor necrosis factor-alpha. 1533 58

Delayed polymorphonuclear leukocyte (PMN) apoptosis exacerbates acute lung injury. To reach the alveolar spaces, PMNs must migrate across both pulmonary endothelial and epithelial cell layers. We hypothesized that transmigration across the endothelium-epithelium bilayer suppresses PMN apoptosis and sought to elucidate the underlying mechanisms. PMNs freshly isolated from normal volunteers were allowed to migrate across polycarbonate membranes alone or membranes coated with a bilayer of human lung endothelial and epithelial cells. After migration toward different chemoattractants (IL-8, formyl-Met-Leu-Phe, or leukotriene B(4)), PMN apoptosis and caspase activities were assessed by annexin V, histology, and enzymatic assays, respectively. Messenger RNA and specific protein expression in three receptor ligand-mediated, apoptosis-inducing pathways (Fas, TNF-alpha, and TNF-related apoptosis-inducing ligand) were further examined by gene array, RT-PCR, flow cytometry, and Western blot analyses. The data demonstrated that transbilayer migration suppressed PMN apoptosis, and this effect was not chemoattractant type specific. Kinetic analyses further showed that the delay of apoptosis was sustained to at least 18 h. Transbilayer migration caused significant decreases in caspase (-3, -8, and -9) activities. The changes in apoptosis-related gene expression support the survival role of transbilayer migration. Furthermore, the reduced apoptosis was correlated with downregulation of Fas ligand and TNF receptor 1 expression. Our data reveal that migration across a lung endothelium-epithelium bilayer suppresses PMN apoptosis. The decreased activity and/or expression of proapoptotic proteins may provide possible targets for the regulation of inappropriate delay in PMN apoptosis during lung inflammation and injury.
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PMID:Regulation of polymorphonuclear leukocyte apoptosis: role of lung endothelium-epithelium bilayer transmigration. 1547 82

Interleukin-8 (IL-8, or CXCL8), which is a chemokine with a defining CXC amino acid motif that was initially characterized for its leukocyte chemotactic activity, is now known to possess tumorigenic and proangiogenic properties as well. In human gliomas, IL-8 is expressed and secreted at high levels both in vitro and in vivo, and recent experiments suggest it is critical to glial tumor neovascularity and progression. Levels of IL-8 correlate with histologic grade in glial neoplasms, and the most malignant form, glioblastoma, shows the highest expression in pseudopalisading cells around necrosis, suggesting that hypoxia/anoxia may stimulate expression. In addition to hypoxia/anoxia stimulation, increased IL-8 in gliomas occurs in response to Fas ligation, death receptor activation, cytosolic Ca(2+), TNF-alpha, IL-1, and other cytokines and various cellular stresses. The IL-8 promoter contains binding sites for the transcription factors NF-kappaB, AP-1, and C-EBP/NF-IL-6, among others. AP-1 has been shown to mediate IL-8 upregulation by anoxia in gliomas. The potential tumor suppressor ING4 was recently shown to be a critical regulator of NF-kappaB-mediated IL-8 transcription and subsequent angiogenesis in gliomas. The IL-8 receptors that could contribute to IL-8-mediated tumorigenic and angiogenic responses include CXCR1 and CXCR2, both of which are G-protein coupled, and the Duffy antigen receptor for cytokines, which has no defined intracellular signaling capabilities. The proangiogenic activity of IL-8 occurs predominantly following binding to CXCR2, but CXCR1 appears to contribute as well through independent, small-GTPase activity. A precise definition of the mechanisms by which IL-8 exerts its proangiogenic functions requires further study for the development of effective IL-8-targeted therapies.
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PMID:The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. 1583 Dec 31

CD40 is expressed on basal keratinocytes and Squamous Cell Cancer of the Head and Neck (SCCHN) tumor cells in vivo and in vitro. CD40 ligation reduces proliferation of SCCHN cell lines and enhances EGFr mediated inhibition of proliferation. We investigated the mechanisms of CD40 function and EGFr cross-communication in SCCHN cell lines. CD40 ligation inhibited spontaneous and Fas-induced apoptosis. CD40 ligation specifically increased the secretion of IL-8, VEGF and PGE(2) but not IL-6, IL-10, FasL, GM-CSF, or TGFalpha. Co-ligation with EGFr further increased IL-8, VEGF and PGE(2) secretion. CD40 ligation also induced delayed activation and tyrosine phosphorylation of EGFr. CD40 induces secretion of specific proinflammatory and proangiogenic cytokines, inhibits spontaneous and Fas-induced apoptosis and increases EGFr phosphorylation. CD40 signaling may enhance the survival of SCCHN and tumor stroma.
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PMID:CD40 function in squamous cell cancer of the head and neck. 1587 50


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