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)

Intestinal mucosal epithelial cells produce IL-8, a neutrophil chemoattractant that contributes to mucosal inflammation in various infectious and inflammatory diseases. However, the mediators involved and the molecular regulation of IL-8 production are poorly understood. As PGE2 is central in gut inflammation and modulates a variety of mucosal epithelial cell functions, we determined whether PGE2 can affect the expression of IL-8. Exogenous PGE2 induced the accumulation of IL-8 mRNA and protein production in a dose- and time-dependent manner in T84 human colonic epithelial cells. Forskolin and dibutyryl cAMP, which increase intracellular cAMP, stimulated IL-8 in a fashion similar to that of PGE2. PGE2 and PGE2 receptor agonists coupling through EP4 receptors elevated intracellular cAMP and up-regulated IL-8 mRNA expression by activating protein kinase A. Unlike PMA, PGE2 and forskolin did not increase IL-8 gene transcription. However, PGE2, forskolin, and PMA enhanced the stability of IL-8 mRNA transcripts, suggesting the involvement of posttranscriptional regulation. Chloramphenicol acetyltransferase reporter gene transfection studies confirmed the presence of a PGE2 responsive cis-element(s) in the IL-8 3' untranslated region. Furthermore, dexamethasone inhibited PGE2-, forskolin-, and dibutyryl cAMP-induced, but not PMA-induced, IL-8 protein production. These results highlight a novel role for PGE2 in up-regulating IL-8 gene expression by colonic epithelial cells, which may contribute to exacerbation of inflammation in the gastrointestinal tract.
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PMID:Prostaglandin E2 stimulates IL-8 gene expression in human colonic epithelial cells by a posttranscriptional mechanism. 975

To examine the production of hepatocyte growth factor (HGF) by human endometrial stromal cells (ESC) in vitro, concentrations of HGF in the culture media of ESC were measured after the addition of various amounts of 12-O-tetradecanoylphorbol 13-acetate (TPA), forskolin, lipopolysaccharide (LPS), interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNFalpha), interferon-gamma (IFNgamma), or ethynylestradiol-17alpha using an ELISA. The expression of HGF mRNA was also assayed by a reverse transcription-polymerase chain reaction. The concentration of HGF in the culture media of unstimulated ESC was below the detection level of the assay. TPA stimulated the secretion of HGF by ESC in a dose-dependent manner. TPA also induced the transcription of HGF mRNA by ESC. Forskolin, LPS, IL-1beta, IL-6, IL-8, TNFalpha, IFNgamma, or ethynylestradiol-17alpha did not alter HGF mRNA or protein levels. TPA-stimulated production of HGF was partially inhibited by the addition of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine or sphingosine. These results suggest that a protein kinase C-dependent pathway may play an important role in the regulation of HGF production by ESC. HGF secreted by ESC may be involved in the regeneration of the endometrium during the normal menstrual cycle.
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PMID:Expression of hepatocyte growth factor in cultured human endometrial stromal cells is induced through a protein kinase C-dependent pathway. 1020 81

To clarify the biological and pathological features of choriocarcinoma, we evaluated the in vitro production of cytokines by a choriocarcinoma cell line, BeWo. We measured the concentration of interleukin (IL)-6 and IL-8 in the culture media of BeWo cells after stimulation with various modulatory agents of cytokine expression by enzyme-linked immunosorbent assays. Northern blot analysis was used to examine the expression of IL-6 and IL-8 mRNA in these cells. A weak expression of IL-6 and IL-8 was detected in unstimulated BeWo cells by both methods. IL-6 transcription and secretion were dose-dependently enhanced by stimulation with IL-1beta, tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1 and 12-O-tetradecanoyl phorbol-13-acetate (TPA). Forskolin, lipopolysaccharide and interferon-gamma had no effect on these cytokines production. The TNF-alpha-induced secretion of IL-6 was inhibited by dexamethasone. The TPA-induced production of IL-6 was inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and sphyngosine, suggesting the involvement of a protein kinase C-dependent pathway. Levels of IL-8 mRNA and protein were also dose-dependently increased by stimulation with IL-1beta, TNF-alpha and TPA. In contrast to IL-6, the expression of IL-8 was not affected by TGF-beta1. It is suggested that, in addition to the production of steroidal and non-steroidal hormones, these cytokines may serve as part of a cytokine network that modulates the proliferation and angiogenesis of choriocarcinomas.
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PMID:Production of interleukin (IL)-6 and IL-8 by a choriocarcinoma cell line, BeWo. 1083 70

It is controversial whether mutations in cystic fibrosis transmembrane conductance regulator intrinsically dysregulate inflammation. We characterized passage 2 human tracheobronchial epithelial cell cultures morphologically and physiologically and determined whether cytokine production or nuclear factor-kappaB activation was systematically altered in cystic fibrosis (CF) cells. Non-CF and CF cells originating from a total of 33 and 25 lungs, respectively, were available for culture on plastic or at an air-liquid interface until well differentiated. Forskolin-stimulated short-circuit currents were present in representative polarized non-CF cultures and were absent in CF cultures, whereas uridine 5'-triphosphate-stimulated currents were present in both. Constitutive or interleukin (IL)-1beta-induced IL-8 or IL-6 secretion or nuclear factor-kappaB activity was not significantly different between non-CF and CF cells. The cytokines regulated upon activation, normal T cell expressed and secreted (RANTES) and IL-10 were not detectable. Stimulation with tumor necrosis factor-alpha or a synthetic toll-like receptor 2 agonist or variable doses and times of Staphylococcus aureus culture filtrate revealed a single dose- and time-dependent difference in IL-8 production by CF cells. Interestingly, although IL-8 secretion after stimulation with Pseudomonas aeruginosa filtrates was not greater in CF cells in the absence of human serum, it was variably greater in its presence. Thus, although exaggerated responses may develop under certain conditions, our results do not support an overall intrinsically hyperinflammatory phenotype in CF cells.
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PMID:Cytokine secretion by cystic fibrosis airway epithelial cells. 1467 Aug