Cytokine Gene Expression Associated with Bone Destruction in Cholesteatoma Tissues

Park, Chul Won; Jang, Young Ho; Yu, Yean Hee; Ahn, Myung Ju

Abstract

BACKGROUND AND OBJECTIVES: Cholesteatoma is composed of hyperproliferative keratinizing epithelium in the middle ear cavity. Although the mechanism of bone destruction by cholesteatoma has not been fully elucidated, it has been reported that activation of several cytokines followed by osteoclast activation might have a major effect on bone resorption in cholesteatoma. Among the several cytokines, it has been suggested that the overexpression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) in the cholesteatomatous tissue is correlated with bone destruction, and transforming growth factor-beta1 (TGF-beta1) and interleukin-4 (IL-4) are associated with osteoclast inhibitory activity. To determine the potential role of several cytokines in the pathogenesis of cholesteatoma and its bone destruction, we investigated mRNA expression of four cytokines in the cholesteatomatous tissue. MAERIALS AND METHODS: We investigated mRNA expression of cytokines in 20 cholesteatomatous tissues as well as in the normal postaural skins using RT-PCR (reverse transcriptase-polymerase chain reaction).
RESULTS
1) Out of 20 cholesteatomatous tissues, six were mRNA expressions of IL-1alpha, four of IL-6, ten of TGF-beta1 mRNA, but no expressions of IL-4. There was no gene expression except six cases for TGF-beta1 in the normal postaural skin. 2) Three cases that expressed IL-1alpha, IL-6, and TGF-beta1 showed severe bone destruction, whereas no bone destruction was noted in 5 cases that expressed only TGF-beta1. 3) There was no significant correlation between the duration of disease and the individual cytokine expression.
CONCLUSION
These findings suggest that IL-1alpha and IL-6 may play a major role in the proliferation and growth of cholesteatoma as well as the excitatory effect for bone destruction by cholesteatoma, and TGF-beta1 might have a protective effect for bone destruction.