caa a22 4500 475848950 CHVBK 20180406123922.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/s004050000249 doi (NATIONALLICENCE)springer-10.1007/s004050000249 Induction of matrix metalloproteinases in keratinocytes by cholesteatoma debris and granulation tissue extracts [Elektronische Daten] [M. Schmidt, P. Grünsfelder, F. Hoppe] Although it is generally accepted that destruction and remodeling of temporal bone associated with middle ear cholesteatoma is mainly caused by the action of osteoclasts, it has been shown that neutral collagenases also play a role in predigesting the osteoid layer and exposing the mineralized bone to osteoclastic activity. Here we show that gelatinase B (matrix metalloproteinase-9) is over-expressed in cholesteatoma compared to external ear canal skin (EACS). Expression of MMP-9 in cholesteatoma mainly occurs in suprabasal layers, and more rarely in basal layers of cholesteatoma epithelium, as well as in inflammatory cells of the perimatrix. We further analyzed the influence of cholesteatoma debris, cholesteatoma granulation tissue, and cholesteatoma components such as keratin, cholesterol and bacterial endotoxin on the expression of MMPs in EACS keratinocytes. We show that cholesteatoma debris and granulation tissue extract both induced the secretion of MMP-9 by EACS keratinocytes, while keratin, bacterial lipopolysaccharide (LPS) or cholesterol did not show any effect. We further performed co-incubation and immunoprecipitation experiments using neutralizing interleukin-1α, EGF, TGF-β, TGF-α, interleukin-6 and TNF-α antibodies. Inhibition of MMP-9 up-regulation by debris or granulation tissue extract could be revealed with diverse cytokine antibodies. The results are discussed with regard to previously published studies. Springer-Verlag Berlin Heidelberg, 2000 Key words Metalloproteinases nationallicence Cholesteatoma nationallicence Zymography nationallicence Cytokine nationallicence Schmidt M. University of Wuerzburg, Department of Otorhinolaryngology, Josef-Schneider-Straße 11, 97080 Wuerzburg, Germany Tel.: +49-931-2012365, Fax: +49-931-2012248 e-mail: marianne.schmidt@mail.uni-wuerzburg.de, DE aut Grünsfelder P. University of Wuerzburg, Department of Otorhinolaryngology, Josef-Schneider-Straße 11, 97080 Wuerzburg, Germany Tel.: +49-931-2012365, Fax: +49-931-2012248 e-mail: marianne.schmidt@mail.uni-wuerzburg.de, DE aut Hoppe F. University of Wuerzburg, Department of Otorhinolaryngology, Josef-Schneider-Straße 11, 97080 Wuerzburg, Germany Tel.: +49-931-2012365, Fax: +49-931-2012248 e-mail: marianne.schmidt@mail.uni-wuerzburg.de, DE aut https://doi.org/10.1007/s004050000249 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004050000249 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schmidt M. University of Wuerzburg, Department of Otorhinolaryngology, Josef-Schneider-Straße 11, 97080 Wuerzburg, Germany Tel.: +49-931-2012365, Fax: +49-931-2012248 e-mail: marianne.schmidt@mail.uni-wuerzburg.de, DE aut NATIONALLICENCE 700 1- Grünsfelder P. University of Wuerzburg, Department of Otorhinolaryngology, Josef-Schneider-Straße 11, 97080 Wuerzburg, Germany Tel.: +49-931-2012365, Fax: +49-931-2012248 e-mail: marianne.schmidt@mail.uni-wuerzburg.de, DE aut NATIONALLICENCE 700 1- Hoppe F. University of Wuerzburg, Department of Otorhinolaryngology, Josef-Schneider-Straße 11, 97080 Wuerzburg, Germany Tel.: +49-931-2012365, Fax: +49-931-2012248 e-mail: marianne.schmidt@mail.uni-wuerzburg.de, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer