M. Schmidt et al., Up-regulation of matrix metalloprotease-9 in middle ear cholesteatoma - correlations with growth factor expression in vivo?, EUR ARCH OT, 258(9), 2001, pp. 472-476
The role of matrix metalloproteases and their regulation in the pathology o
f middle ear cholesteatoma is still unclear. Recently we have demonstrated
that incubation of keratinocytes with cholesteatoma debris and granulation
tissue extracts causes induction of gelatinase B (matrix metalloproteinase-
9, MMP-9) secretion in vitro. Antibodies against a variety of growth factor
s revealed some inhibitory effect on MMP-9 induction, caused by debris or g
ranulation tissue extracts. In order to investigate the coherence of growth
factor expression and matrix metalloproteinase activity in vivo in middle
ear cholesteatoma, we performed quantitative gelatin zymographic analysis w
ith tissue homogenates of 37 cholesteatoma and nine external ear canal skin
(EACS) samples. Furthermore we quantified levels of the cytokines IL-1 alp
ha, IL-1 beta, TNF-alpha, TGF-beta and EGF present in tissue extracts, usin
g enzyme-linked immunosorbent assays (ELISA), and correlated cytokine conce
ntrations with gelatinolytic activities. Zymographic analysis revealed a hi
ghly heterogeneous expression of gelatinase A and B in cholesteatoma specim
ens. As shown previously, MMP-9, but not MMP-2, was increased in cholesteat
oma when compared to EACS samples. ELISA studies revealed a significantly e
levated IL-1 alpha level in cholesteatoma. Regression analysis involving ge
latinolytic activity and cytokine concentrations in tissue homogenates show
ed no statistically significant correlation between expression of gelatinas
es and the cytokines IL1-alpha, IL1-beta, TNF-alpha, TGF-beta or EGF. The d
iscrepancy between in vitro observations and the situation in vivo is discu
ssed critically.