Cathepsin L activity and its inhibitor in human otitis media

Objective: We examined cathepsin L activity, expression of cystatin A, and copper- and zinc-containing superoxide dismutase in human chronic otitis media. The relationships of our findings to clinical findings (e.g., grade of bone destruction) were also studied. Design: Retrospective basic and clinical study. Setting: Department of Otolaryngology and First Department of Biochemistry, Kinki University School of Medicine, Osaka, Japan. Method: The human middle ear tissues evaluated in this study were surgically obtained from seven patients with cholesteatoma epithelium, three patients with granulation tissues in cholesteatoma, three patients with granulation tissues in noncholesteatoma, and three patients with intact mucous membrane of the middle ear. Main Outcome Measures: Cathepsin L activities in cholesteatoma epithelium, granulation tissues in cholesteatoma, or granulation tissues in noncholesteatoma were measured using Barrett's method. Cystatin A expressions were observed by Western blot analysis. Copper- and zinc-containing superoxide dismutase in cholesteatoma was examined immunohistochemically. Results: Mean cathepsin L activity was higher in diseased tissues than in intact mucous membranes of the middle ear. Granulation tissues with high cathepsin L activity resulted in extensive bone destruction in both cholesteatomas and non-cholesteatomas of the middle ear. All cases with intact mucous membrane of the middle ear exhibited no expression of cystatin A. Seven of 10 cases with diseased tissues expressed cystatin A in cholesteatoma epithelium, granulation tissues in cholesteatoma, or granulation tissues in noncholesteatoma. No relationships were found between cystatin A expression and grade of cathepsin L activity. Copper- and zinc-containing superoxide dismutase was more strongly positive in cholesteatoma epithelium regions than in granulation tissues. Conclusion: These results suggest that copper- and zinc-containing superoxide dismutase in cholesteatoma epithelium prevents complications by suppressing cathepsin L activity.