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) 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. SUBJECTS: 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.
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) 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. SUBJECTS: 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: Ariadne Letra; Walid Fakhouri; Renata F Fonseca; Renato Menezes; Inga Kempa; Joanne L Prasad; Toby G McHenry; Andrew C Lidral; Lina Moreno; Jeffrey C Murray; Sandra Daack-Hirsch; Mary L Marazita; Eduardo E Castilla; Baiba Lace; Ieda M Orioli; Jose M Granjeiro; Brian C Schutte; Alexandre R Vieira Journal: PLoS One Date: 2012-09-20 Impact factor: 3.240
Authors: Kuen Yao Ho; Tai Sheng Yeh; Han Hsiang Huang; Kuo Feng Hung; Chee Yin Chai; Wan Tzu Chen; Shih Meng Tsai; Ning Chia Chang; Chen Yu Chien; Hsun Mo Wang; Yu Jen Wu Journal: Int J Mol Sci Date: 2013-07-11 Impact factor: 5.923