Expression of Tumor Necrosis Factor-Like Weak Inducer of Apoptosis in Human Middle Ear Cholesteatoma

Abstract

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) was recently identified as a member of the TNF superfamily of structurally related cytokines. It regulates TNF-alpha and numerous cellular responses. We investigated whether TWEAK is upregulated in human middle ear cholesteatoma compared to the skin of the normal external auditory canal (EAC). The expression of TWEAK was analyzed using reverse transcription-polymerase chain reaction, Western blotting and immunohistochemical staining. TWEAK expression was correlated with that of TNF-alpha as determined by Western blotting. The expression of TWEAK and TNF-alpha protein was stronger in cholesteatoma tissue than in EAC skin. TWEAK was expressed to a greater degree in the suprabasal layer in the cholesteatoma than in EAC skin. The expression of TWEAK was correlated more closely with single-stranded DNA than Ki-67 immunohistochemically. These findings imply that TWEAK plays an important role in modulating TNF-alpha expression and apoptosis in cholesteatoma. (C) 2013 S. Karger AG, Basel