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Regulation of interleukin-6 (IL-6) expression: Evidence for a tissue-specific role of protein kinase C

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Abstract

The regulation of IL-6 mRNA expression was studied in human blood monocytes and in the human epidermoid carcinoma cell line HEp-2. In human monocytes phorbol-12-myristate 13-acetate (PMA) did not induce IL-6 but it increased IL-1β and IL-8 mRNA levels. Furthermore, in monocytes, protein kinase C (PKC) activation by PMA even reduced IL-1-induced IL-6 mRNA, and IL-1-induced IL-6 synthesis was increased by the PKC inhibitor staurosporine. IL-6 synthesis in HEp-2 cells was induced by IL-1, PMA, and calcium ionophore A 23187 but not by dibutyryl-cAMP. PMA-, but not IL-1-induced IL-6 synthesis in HEp-2 cells was inhibited by staurosporine. PMA pretreatment of HEp-2 cells abolished PMA-induced IL-6 but the IL-1 effect was not reduced. These data indicate that IL-6 can be induced by a PKC-independent pathway in monocytes and HEp-2 cells. In monocytes PKC activation does not induce IL-6 and PMA interferes with the IL-1 effect. Transcription factors known to be involved with the regulation of IL-6 expression were studied by gel retardation assays. NF-IL-6 and AP-1 activity were constitutively expressed in monocytes and HEp-2 cells under conditions where IL-6 mRNA was not detectable and levels did not change in response to stimulation by IL-1 or PMA. In contrast, NF-kB was increased by both IL-1 and PMA, but only the effect of PMA, and not that of IL-1, was inhibited by staurosporine. In summary, these results show tissue-specific differences in the regulation of IL-6 expression. Induction of IL-6 in monocytes is PKC independent. In the epithelial cell line HEp-2 IL-6 is inducible by PKC as well as by a PKC-independent pathway.

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Authors and Affiliations

  1. Sam and Rose Stein Institute for Research on Aging and the Department of Medicine, University of California San Diego, 92093, La Jolla, California

    Volker Gross, Baoping Zhang, Yu Geng, Peter M. Villiger & Martin Lotz

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  1. Volker Gross
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  2. Baoping Zhang
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  3. Yu Geng
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  4. Peter M. Villiger
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  5. Martin Lotz
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Gross, V., Zhang, B., Geng, Y. et al. Regulation of interleukin-6 (IL-6) expression: Evidence for a tissue-specific role of protein kinase C. J Clin Immunol 13, 310–320 (1993). https://doi.org/10.1007/BF00920239

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  • DOI: https://doi.org/10.1007/BF00920239

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