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)

Levels of messenger RNA (mRNA) extracted from five samples of radicular cyst-lining epithelium were analyzed for cytokines, growth factors and epithelial cell growth-related receptors by RT-PCR. All five samples expressed IL-1alpha, -1beta, IL-6, IL-8, IL-11, TGF-beta1, PDGF-A and aFGF, and receptors for EGF (c-erbB), KGF, HGF (c-met) and IL-6. Some of the specimens expressed MIP-1alpha, RANTES, GM-CSF, M-CSF, TNF-alpha, PDGF-B and bFGF, but no expression of IL-2, IL-4, IFN-gamma, IGF-I, EGF and KGF was detected. These results indicate that radicular cyst-lining epithelium, which is considered to be identical to the cell rests of Malassez, may play a role in periodontal pocket formation or apical cyst formation by interaction with surrounding connective tissue or hematopoietic cells through the expression of various cytokines.
 ...
PMID:Profiles of cytokine expression in radicular cyst-lining epithelium examined by RT-PCR. 1126 83

In order to study embryogenesis and organogenesis in vitro, two cell mouse embryos were cultured with alpha-MEM supplemented 10% FCS and embryotrophic factors (ETFs). The ETFs were separated from the conditioned medium of a SKG-II-SF cell line derived from a human uterine cervical epidermoid carcinoma. IL-1 beta, IL-6, IL-8, EGF, GH, PDGF-AB, basic FGF, VEGF were also detected in the conditioned media of this cell line. Using ETFs and a 10% FCS supplemented culture medium, 23% of the mouse two cell stage embryos developed to the bilaminar disc stage, 13% to the trilaminar germ disc stage, 9% were observed with blood islets in the yolk sac, and the heart beat was noted in 7% (28 embryos) of the embryos. Furthermore, primordial organs, such as the liver, heart, kidney, notochord, retina-like structure, etc. were observed. Usually, structures associated with the primordial streak stage (bilaminar germ disc embryo) developed in vitro using ETFs from two cell stage embryos. These closely resemble structures found at the same stage in the normal embryo in vivo. After the primordial streak stage, the cultured embryos showed no resemblance to the same stage in normal embryos. None of the external appearances of these embryos appeared normal. On the other hand, trilaminar disc stage embryos never developed when using only a 10% FCS supplemented culture system.
 ...
PMID:Effects of embryotrophic factors on the embryogenesis and organogenesis of mouse embryos in vitro. 1132 34

The matrix metalloproteinases, MMP-2 and MMP-9, are known to be critical extracellular-remodeling enzymes in wound healing and other diseases of the ocular surface. This study investigated the regulation of MMP-2 and MMP-9 in human corneal epithelial cells by growth factors and pro-inflammatory cytokines (IL-1beta and TNF-alpha) they are exposed to, and by doxycycline, a medication used to treat ocular surface disease. Primary human corneal epithelial cell cultures were treated with one of the following cytokines (IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha) or growth factors (EGF, HGF, KGF, PDGF-BB, TGF-alpha, TGF-beta), with or without their corresponding inhibitors. The conditioned media were collected after 24 hr for gelatin zymography and MMP-9 activity assay. Total RNA was extracted from the cells treated for 6 hr and was subjected to RT-PCR and Northern hybridization. Between the two gelatinases, MMP-2 and MMP-9, detected by zymography, the 92 kDa MMP-9 in the conditioned medium was markedly up-regulated by the pro-inflammatory cytokines, IL-1beta and TNF-alpha. The MMP-9 protein and activity were dose-dependently stimulated by IL-1beta or TNF-alpha at 0.1, 1.0 and 10 ng ml(-1). This up-regulation was nearly abolished by neutralizing antibodies (IL-1beta and TNF-alpha) and by IL-1 receptor antagonist. Semi-quantitative RT-PCR and Northern hybridization disclosed that the MMP-9 transcript was also markedly up-regulated in a dose-dependent manner by IL-1beta and TNF-alpha. Doxycycline (10 microg ml(-1)) suppressed MMP-9 protein level and activity, but not its mRNA, that was stimulated by IL-1beta and TNF-alpha (1 ng ml(-1)). In contrast, the 72 kDa MMP-2 was not significantly modulated by any of these cytokines. In conclusion, production of MMP-9 is stimulated by the pro-inflammatory cytokines, IL-1beta and TNF-alpha. These factors may play a role in the pathogenesis of MMP-9 mediated corneal matrix degradation. The efficacy of doxycycline in treating ocular surface diseases may be related to its ability to suppress MMP-9 production in the corneal epithelium.
 ...
PMID:Regulation of MMP-9 production by human corneal epithelial cells. 1182 17

Epidermal growth factor receptor (EGFR) tyrosine kinase is a potential target for anticancer therapy. ZD1839 (Iressa) is a selective inhibitor of EGFR tyrosine kinase. In this study, we investigated the question as to whether the antitumor effect of ZD1839 is partly attributable to antiangiogenic activity and the potential mechanisms involved. Both ZD1839 and SU5416 [a vascular endothelial growth factor (VEGF)-receptor tyrosine kinase inhibitor] inhibited the migration of human umbilical vein endothelial cell cocultivated with EGF-stimulated cancer cells. ZD1839 also inhibited EGF-induced migration and the formation of tube-like structures by human microvascular endothelial cells. Moreover, ZD1839 almost completely blocked EGF-induced neovascularization of mice cornea, and SU5416 partially blocked neovascularization. In contrast, ZD1839 did not inhibit VEGF-induced angiogenesis. However, EGF-induced up-regulation of the angiogenic factors, VEGF and IL-8, was almost completely blocked by ZD1839. The antitumor effects of ZD1839 could, therefore, be mediated in part by the inhibition of tumor angiogenesis through direct effects on microvascular endothelial cells that express EGFR and also through reduced production of proangiogenic factors by tumor cells.
 ...
PMID:ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. 1198 Jun 49

Cytokines (IL-1, IL-6, IL-8, IL-11, TNF, IFN-gamma, and TGF-beta) and growth factors (EGF, bFGF, aFGF, and KGF) play an important role in modulation of hormone secretion by directly influencing specific enzyme steps of steroidogenesis in various endocrine cell types. For this tabular data collection, the following enzyme steps were considered: steroidogenic acute regulatory protein (StAR), side chain cleavage enzyme (P450scc), 3 beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase/17,20-lyase (P450c17), 17-beta-hydroxysteroid-dehydrogenase, aromatase complex, 5-alpha-reductase, P450c21, DHEAS sulfatase, and DHEA sulfotransferase. This collection summarizes the current information on how the mentioned cytokines and growth factors influence particular enzyme steps.
 ...
PMID:Influence of cytokines and growth factors on distinct steroidogenic enzymes in vitro: a short tabular data collection. 1211 70

The blood-brain barrier (BBB) mediates interactions between the brain and the cytokines produced in the periphery. Some of these cytokines play significant roles in feeding behavior. This review will summarize various ways by which cytokines cross the BBB and discuss the implications of their transport systems in feeding. For simplicity of discussion, three categories of cytokines are discussed: (1). the proinflammatory cytokines TNFalpha, IFNgamma, IL1, and IL6; (2). the chemokines MIP-1, CINC-1 and IL8; and (3). other cytokines (LIF, CNTF, GM-CSF, FGF, EGF, and TGFalpha). The pharmacokinetics of barrier penetration, compartmental distribution, stability, and mechanism of passage (presence or absence of saturable transport) are summarized. Our understanding of cytokines interacting with the BBB is still growing; not only are more cytokines being studied, but also more details of the nature of the transport systems and how they affect feeding behavior are being explored.
 ...
PMID:Interactions of cytokines with the blood-brain barrier: implications for feeding. 1267 82

Toll-like receptors (TLRs) activate antimicrobial gene expression in response to detection of specific bacterial products. Relatively little is known about TLR5, the only TLR thought to be preferentially expressed by epithelial cells, beyond that it confers activation of the transcription factor NF-kappaB in a MyD-88 dependent manner in response to flagellin. Because TLRs, in general, are also thought to signal through members of the MAPK family, we examined flagellin-induced MAPK activation (via examining its phosphorylation status) and its subsequent role in expression of the chemokine IL-8 in polarized intestinal epithelia. Flagellin, like other proinflammatory stimuli (TNF-alpha, Salmonella typhimurium), activated p38 MAPK in a TLR5-dependent manner, whereas aflagellate bacteria or EGF did not activate this kinase. Although ERK1 and -2 were also observed to be activated in response to flagellin, their activation was not restricted to proinflammatory stimuli because they were also potently activated by aflagellate bacteria (S. typhimurium or Escherichia coli) and EGF (neither of which activate NF-kappaB in these cells). Pharmacological inhibition of p38 MAPK (by SB-203580) potently (IC50 = 10 nM) reduced expression of IL-8 protein (maximal inhibition, 75%) but had no effect on NF-kappaB activation, only slightly attenuated upregulation of IL-8 mRNA levels in response to flagellin, and did not effect IL-8 mRNA stability. Together, these results indicate that epithelial TLR5 mediates p38 activation and subsequently regulates flagellin-induced IL-8 expression independently of NF-kappaB, probably by influencing IL-8 mRNA translation.
 ...
PMID:TLR5-mediated activation of p38 MAPK regulates epithelial IL-8 expression via posttranscriptional mechanism. 1270 97

In vivo models utilizing orthotopic injection of tumor cells into nude mice have proven valuable for the study of metastasis. However, breast cancers are among the more difficult of human tumors to grow in immunodeficient mice, with a relatively low tumor take. Fewer still develop spontaneous metastases. The injection of GI101A breast cancer cells into the mammary fatpad (mfp) produced lung metastases in 25% of tumor-bearing mice. Selecting cells from the lung metastases and recycling in vivo resulted in the isolation of a series of variant cell lines. These cell lines were tested for tumorigenicity and metastasis in nude mice following mfp injection compared with the original cell line, and in vitro expression of factors associated with the metastatic phenotype measured. The in vivo selected cell lines were more aggressive, with higher tumor take, faster local growth rate and increased incidence (> or = 85%) and extent of lung metastasis. However, the metastasis-selected variants showed no increases in expression of the growth factor receptors EGFR or HER-2, and the pro-angiogenic factors VEGF-A and IL-8. Immunohistochemistry of mfp tumors revealed no differences in microvessel density (counting CD-31 positive structures) and cell proliferation (PCNA-positive cells) comparing the GI101A line with selected variants. No TUNEL-positive cells were detected in the tumors of the metastasis-derived variant, with a small number of cells undergoing apoptosis detected in sections of GI101A tumors. In vitro, the metastasis-derived variants were found to have a more robust expression of phosphorylated PKB/Akt, with or without EGF or serum stimulation, suggesting an association between Akt activation and metastatic ability. This new series of isogenic cell lines may be valuable for identifying molecular mechanisms involved in the metastatic progression of breast cancer.
 ...
PMID:Selection of more aggressive variants of the gI101A human breast cancer cell line: a model for analyzing the metastatic phenotype of breast cancer. 1459 85

Many cells upon injury mount extensive, compensatory responses that increase cell survival; however, the intracellular signals that regulate these responses are not completely understood. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been implicated as a cytoprotective agent. We have previously demonstrated that pretreatment of human intestinal epithelial cells with HB-EGF significantly decreased cytokine-induced activation of inducible NO synthase mRNA expression and NO production and protected the cells from apoptosis and necrosis. However, the mechanisms by which HB-EGF exerts these effects are not known. Here we show that cytokine exposure (IL-1beta and IFN-gamma) induced NF-kappaB activation and IL-8 and NO production in DLD-1 cells. Transient expression of a dominant negative form of IkappaBalpha decreased NO production, suggesting that the cytokines stimulated NO production in part through activation of NF-kappaB. HB-EGF dramatically suppressed NF-kappaB activity and IL-8 release and decreased NO production in cells pretreated with HB-EGF. HB-EGF blocked NF-kappaB activation by inhibiting IkappaB kinase activation and IkappaB phosphorylation and degradation, thus interfering with NF-kappaB nuclear translocation, DNA-binding activity, and NF-kappaB-dependent transcriptional activity. The data demonstrate that HB-EGF decreases inflammatory cytokine and NO production by interfering with the NF-kappaB signaling pathway. Inhibition of NF-kappaB may represent one of the mechanisms by which HB-EGF exerts its potent anti-inflammatory and cytoprotective effects.
 ...
PMID:Inhibition of NF-kappa B activation and its target genes by heparin-binding epidermal growth factor-like growth factor. 1463 13

Autotaxin (ATX/NPP2) is a tumor cell motility-stimulating factor that displays both a nucleotide pyrophosphatase/phosphodiesterase activity and a recently described lysophospholipase D (lysoPLD) activity. The precise function of ATX in tumor cells and the role of ATX in thyroid carcinoma remains unclear. We have quantified ATX mRNA expression in thyroid carcinoma cell lines and in tissues of patients with thyroid carcinomas. ATX gene activity was significantly higher in undifferentiated anaplastic thyroid carcinoma cell lines (UTC) and tumor tissues as compared to follicular thyroid carcinoma (FTC) cell lines, FTC tissues or goiter tissues that were used as a control. In the thyroid carcinoma cell line 1736, EGF and bFGF stimulated ATX mRNA expression, whereas the cytokines IL-4, IL-1beta and TGF-beta reduced ATX transcriptional levels. FTC-133 cells, stably transfected with an expression vector for ATX, showed a higher lysoPLD activity, a higher proliferation rate and an increased migratory behavior. In addition, ATX also displayed a paracrine stimulatory effect on the motility of different thyroid carcinoma cell lines. Overexpression of ATX in the stably transfected FTC-133 resulted in down-regulation of CD54/ intercellular adhesion molecule-1 (ICAM-1) gene expression and augmented gene activity of the pro-angiogenic chemokine IL-8. We conclude that ATX may be regarded as a new tissue marker for undifferentiated human thyroid carcinoma cells. ATX increases the proliferation and migration of thyroid carcinoma cell lines and may also affect the angiogenic potential of thyroid carcinoma cells. Further studies are needed to provide insight into the role of ATX in the normal and neoplastic thyroid gland.
 ...
PMID:Expression, regulation and function of autotaxin in thyroid carcinomas. 1502 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>