Germany: Stem cells in cholesteatoma are cellular mediators of its highly pro-inflammatory environment

Stem Cell-Induced Inflammation in Cholesteatoma Is Inhibited by the TLR4 Antagonist LPS-RS

Mathias Schurmann, Johannes Greiner, Verena Volland-Thurn, Felix Oppel, Christian Kaltschmidt, Holger Sudhoff and Barbara Kaltschmidt|Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, 33604 Bielefeld, Germany; Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany; AG Molecular Neurobiology, University of Bieldefeld, 33619 Bielefeld, Germany|cells|2020| 9, 199; doi:10.3390/cells9010199

Cholesteatoma is a severe non-cancerous lesion of the middle ear. Pathogenic stem cells have previously been demonstrated within cholesteatoma tissue, with their roles in regulating disease-specific chronic inflammation still unknown. The aim of this study was to determine the cellular mediators of the highly pro-inflammatory environment in cholesteatoma. Cholesteatoma stem cells (ME-CSCs) were isolated and treated with lipopolysaccharides (LPS), tumor necrosis factor a (TFNa), and the TLR4-antagonist LPS from R. spheroids (LPS-RS) followed by gene expression analysis using qPCR on Mic qPCR Cycler. GAPDH was used for normalization of cycle threshold values. ME-CSCs showed an increased expression of TLR4. There was also increase in the LPS-dependent pro-inflammatory gene expression pattern of TNFa, IL-1a, IL-1b, IL-6 and IL-8 in ME-CSCs compared to non-pathogenic controls. This study showed that ME-CSCs mediate the inflammatory environment of cholesteatoma via TLR4-mediated NF-kB-signalling. This suggests that ME-CSCs act as drivers of cholesteatoma progression and TLR4 on ME-CSCs.

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