The accumulation of desquamated keratinizing squamous epithelial cells appears to be a crucial factor in the pathogenesis of middle ear cholesteatomas. The accumulation of keratin debris is due to the proliferation and the terminal differentiation of basal keratinocytes. Since cholesteatomas are usually associated with inflammatory reactions in the middle ear cavity, we examined the effects of a granulation tissue conditioned medium on the terminal differentiation of basal keratinocytes in vitro. This conditioned medium stimulated the terminal differentiation of basal keratinocytes by showing: (a) increased incorporation of 3H-leucine into cell envelopes; (b) an increased number of SDS-insoluble cell envelopes; and (c) increased transglutaminase activity (as a marker for terminal cellular differentiation). Our present studies further suggest that inflammatory granulation tissue plays an important role in the clinical growth and development of the cholesteatoma.
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