Identification of specific gene expression profiles in fibroblasts derived from middle ear cholesteatoma.
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.
Yoshikawa
Mamoru
M
Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan. yoshikawa@jikei.ac.jp
Kojima
Hiromi
H
Wada
Kota
K
Tsukidate
Toshiharu
T
Okada
Naoko
N
Saito
Hirohisa
H
Moriyama
Hiroshi
H
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
D007375:Interleukin-1; D012333:RNA, Messenger