title: Identification of specific gene expression profiles in fibroblasts derived from middle ear cholesteatoma.
abstract: OBJECTIVE
  To investigate the role of fibroblasts in the pathogenesis of cholesteatoma.
  
  
  METHODS
  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) 1alpha and/or IL-1beta 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.
  
  
  METHODS
  Six patients who had undergone tympanoplasty.
  
  
  RESULTS
  The IL-1alpha-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 alpha) were more strongly up-regulated by IL-1alpha and/or IL-1beta 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.
authors.affiliation: Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan. yoshikawa@jikei.ac.jp
authors.forename: Mamoru
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kojima
authors.forename: Kota
authors.initials: K
authors.lastname: Wada
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Tsukidate
authors.forename: Naoko
authors.initials: N
authors.lastname: Okada
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moriyama
mesh_terms: D018424:Cholesteatoma, Middle Ear / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger