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Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes.

Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. Research Abstract Details 

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  • Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. Abstract Text:

    hwa-jeong leeHwa-Jeong Lee,jun leeJun Lee,sun-kyung leeSun-Kyung Lee,suk-keun leeSuk-Keun Lee,eun-cheol kimEun-Cheol Kim,hwa-jeong leeHwa-Jeong Lee,jun leeJun Lee,sun-kyung leeSun-Kyung Lee,suk-keun leeSuk-Keun Lee,eun-cheol kimEun-Cheol Kim,

    BACKGROUND: Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO). METHODS: IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-kappaB binding activity. Phosphorylation and degradation of the I-kappaB were analyized by Western blot. RESULTS: IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1beta to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IkappaB, and activation of NF-kappaB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase. CONCLUSION: This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions.

    Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. Publishing Authors By Initials

    hj leeHJ Lee,j leeJ Lee,sk leeSK Lee,sk leeSK Lee,ec kimEC Kim,hj leeHJ Lee,j leeJ Lee,sk leeSK Lee,sk leeSK Lee,ec kimEC Kim,

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    Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: BMC cancer

    VOLUME: 7

    Page Numbers: 176

    Journal Abbreviation: BMC Cancer

    ISSN: 1471-2407

    DAY: 13

    MONTH: 09

    YEAR: 2007

    Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. Information

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    LANGUAGE: eng

    NlmUniqueID: 100967800

    Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. Keywords Mesh Terms:

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    Grant and Affiliation Information for Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes.

    AFFILIATION: Department of Oral & Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea. lhj0506@hotmail.com

    Country: England

    England Research PublicationEngland Research Publication

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    MEDLINETA: BMC Cancer

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