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Compounds that Inhibit Cytokine-Induced Interleukin-6 Expression in a Monocytic Cell Line

Hu, Yuli
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1420708103

Abstract Details

2015, Master of Science (MS), Ohio University, Biomedical Engineering (Engineering and Technology).
Inhibiting Interleukin (IL)-6, a cytokine associated with inflammation, is an established therapeutic target for inflammatory diseases. In this study, we probe the hypothesis that two novel small organic compounds inhibit Tumor Necrosis Factor-alpha (TNF-α) and Interferon-gamma (IFN-γ)-induced IL-6 expression in an undifferentiated human monocytic cell line (THP-1) and freshly isolated monocytes from human peripheral blood. TC50, IC50, and TI values are determined. TC50 is the compound concentration at which the metabolic signal is decreased by 50% relative to carrier (DMSO) control treated cells. IC50 value is the compound concentration at which IL-6 production is inhibited by 50% relative to carrier control treated cells. Therapeutic index (TI) is the TC50 value divided by the IC50 value. The combination of TNF-α and IFN-γ induced IL-6 expression in undifferentiated THP-1 cells. The compounds inhibited the cytokine-induced IL-6 expression at both the gene and the protein levels. The IC50 values for the first compound were 9.4 μM at the gene expression level and 5.8 μM at the protein expression level for 24-hour TNF-α and IFN-γ-induced IL-6 in undifferentiated THP-1 cells. The IC50 values for the second compound were 13.6 μM at the gene expression level and 10.5 μM at the protein expression level. The TC50 values were 79.8 μM and 312.2 μM respectively for undifferentiated THP-1 cells treated for 24 hours with the first compound and the second compound respectively. The TI values for the first compound were 8.5 at the gene expression level and 13.8 at the protein expression level for 24-hour TNF-α and IFN-γ- induced IL-6 in undifferentiated THP-1 cells. The TI values for the second compound were 23.0 at the gene expression level and 29.7 at the protein expression level. The combination of TNF-α and IFN-γ does not appear to induce IL-6 protein expression in freshly isolated monocytes from human peripheral blood. Flow cytometric analysis suggested that freshly isolated monocytes express little, if any, TNF receptor 1, TNF receptor 2, and perhaps a small amount of IFN-γ receptor. However, due to the high signal of IgG2a isotype control binding to the monocytes, it is difficult to draw a firm conclusion regarding the expression of these receptors. In conclusion, this study provides evidence that two novel small organic compounds inhibit TNF-a and IFN-γ-induced IL-6 expression at both the gene and protein levels in undifferentiated THP-1 cells.
Douglas Goetz (Advisor)
Monica Burdick (Committee Member)
Kelly McCall (Committee Member)
Stephen Bergmeier (Committee Member)
Biomedical Engineering
Interleukin-6

Recommended Citations

Citations

  • Hu, Y. (2015). Compounds that Inhibit Cytokine-Induced Interleukin-6 Expression in a Monocytic Cell Line [Master's thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1420708103

    APA Style (7th edition)

  • Hu, Yuli. Compounds that Inhibit Cytokine-Induced Interleukin-6 Expression in a Monocytic Cell Line. 2015. Ohio University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1420708103.

    MLA Style (8th edition)

  • Hu, Yuli. "Compounds that Inhibit Cytokine-Induced Interleukin-6 Expression in a Monocytic Cell Line." Master's thesis, Ohio University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1420708103

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Ohio University and OhioLINK.