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Mamoru Yoshikawa, MD, PhD; Hiromi Kojima, MD, PhD; Kota Wada, MD; Toshiharu Tsukidate, MD; Naoko Okada, BS; Hirohisa Saito, MD, PhD; Hiroshi Moriyama, MD, PhD

Arch Otolaryngol Head Neck Surg. 2006;132:734-742.

Objective  To investigate the role of fibroblasts in the pathogenesis of cholesteatoma.

Design  Tissue specimens were obtained from our patients. Middle ear cholesteatoma–derived fibroblasts (MECFs) and postauricular skin–derived fibroblasts (SFs) as controls were then cultured for a few weeks. These fibroblasts were stimulated with interleukin (IL) 1 and/or IL-1 before gene expression assays. We used the human genome U133A probe array (GeneChip) and real-time polymerase chain reaction to examine and compare the gene expression profiles of the MECFs and SFs.

Subjects  Six patients who had undergone tympanoplasty.

Results  The IL-1–regulated genes were classified into 4 distinct clusters on the basis of profiles differentially regulated by SF and MECF using a hierarchical clustering analysis. The messenger RNA expressions of LARC (liver and activation-regulated chemokine), GMCSF (granulocyte-macrophage colony-stimulating factor), epiregulin, ICAM1 (intercellular adhesion molecule 1), and TGFA (transforming growth factor ) were more strongly up-regulated by IL-1 and/or IL-1 in MECF than in SF, suggesting that these fibroblasts derived from different tissues retained their typical gene expression profiles.

Conclusions  Fibroblasts may play a role in hyperkeratosis of middle ear cholesteatoma by releasing molecules involved in inflammation and epidermal growth. These fibroblasts may retain tissue-specific characteristics presumably controlled by epigenetic mechanisms.

Author Affiliations: Department of Otorhinolaryngology, Jikei University School of Medicine (Drs Yoshikawa, Kojima, Wada, Tsukidate, and Moriyama), and Department of Allergy and Immunology, National Research Institute for Child Health and Development (Ms Okada and Dr Saito), Tokyo, Japan.