In vitro cholesteatoma growth and secretion of cytokines

Helgaland, Tore; Engelen, Bart; Olsnes, Carla; Aarstad, Hans Jørgen; Vassbotn, Flemming S.

doi:10.3109/00016480903413657

Cited by 12 publications

(6 citation statements)

References 15 publications

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“…and Helgaland et al . 34 , 35 , who reported that in vitro growth of cholesteatoma cells is faster than that of cells derived from normal EAC skin, our results showed a lower proliferation of cholesteatoma cells than normal skin cells. This finding is in agreement with other studies where cholesteatoma-derived cells demonstrated lower colony-forming efficiency, fewer passages, and a shorter lifespan compared with normal skin–derived cells 35 – 37 .…”

Section: Discussionsupporting

confidence: 57%

Comparison of changes in mitochondrial bioenergetics between keratinocytes in human external auditory canal skin and cholesteatomas from normoxia to hypoxia

Shih

Lee

Chen

et al. 2018

Sci Rep

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Cholesteatoma has attracted many studies seeking to uncover its nature and the pathogenesis of related diseases. However, no researchers have explored the mitochondrial bioenergetics of cholesteatoma. The aim of this study was to investigate the energy demand and differential mitochondrial respiration profiles between keratinocytes in external auditory canal (EAC) skin and cholesteatoma samples cultured in normoxic (20% O 2 ) and hypoxic (5% O 2 ) conditions. Enhanced cellular proliferation of both types of keratinocytes was found in hypoxia compared to normoxia. In 20% O 2 conditions, cholesteatoma keratinocytes exhibited less mitochondrial mass, lower ATP levels, and significantly lower basal oxygen consumption rate (OCR) and reserve capacity compared to normal skin keratinocytes. In contrast, in hypoxic conditions, cholesteatoma keratinocytes showed markedly higher levels in maximal OCR and reserve capacity, as well as lower proton leak OCRs, compared to normal skin keratinocytes. Hypoxia induced the reverse mitochondrial bioenergy profile from that in normoxia between these two types of keratinocytes, implying that an adaptive change of mitochondrial respiration to oxygen fluctuations may develop in cases of cholesteatoma. Such adaptation in response to hypoxic conditions may play a role in explaining the pathogenesis of acquired cholesteatoma.Cholesteatoma derives from an abnormal growth of the keratinizing squamous epithelium, which consists of a thin layer of stratified squamous epithelium (matrix) and an adjacent subepithelial connective tissue layer (perimatrix) 1 . The enzymatic activity from matrix components (such as collagenase, plasminogen, and N-acetyl-β-hexosaminidase), the local chronic inflammation-recruited osteoclasts, and the inflammatory mediators concomitant with the disease are responsible for its destruction of the bony external auditory canal (EAC) and ossicular chain 2-7 , resulting in refractory otorrhea and progressive hearing loss. Moreover, vertigo and balance dysfunction can be associated when the labyrinth is involved. Although surgical treatment can cure such disease, a wide range of recidivism rates, from 4 to 61%, has been reported [8][9][10] ; thus, the long-term eradication of cholesteatoma remains a great challenge for otologists.Previous studies have investigated whether there is an interaction between cholesteatoma and normal skin of the EAC by comparing their gene regulation, biochemical presentation, and cytokine secretion. Cholesteatomas exhibit increased expression of epidermal growth factor receptor (EGFR), transforming growth factor-α (TGF-α), c-jun, and c-myc, accompanied by a significant upregulation of inflammation-related genes and downregulation of several tumor suppressor genes [11][12][13][14][15][16][17][18][19] . Using whole human genome DNA microarray analysis, the expression profiles of cholesteatomas were demonstrated to mimic those of metastatic tumors and chronically inflamed tissue 14 . The more extensive expression of hyperproliferation-associated cy...

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Section: Discussionsupporting

confidence: 57%

Comparison of changes in mitochondrial bioenergetics between keratinocytes in human external auditory canal skin and cholesteatomas from normoxia to hypoxia

Shih

Lee

Chen

et al. 2018

Sci Rep

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“…We previously discovered that the expression of IL‐6 and p‐STAT3 were significantly higher in cholesteatoma epithelium than in normal external auditory canal epithelium . Helgaland et al discovered an obviously elevated secretion of IL‐6 in cholesteatoma epithelial cells in vitro . In addition, Ho et al found that up‐regulation of STAT3 was presented in cholesteatoma tissues .…”

Section: Cell Proliferation Signal Pathwaysmentioning

confidence: 98%

Acquired cholesteatoma epithelial hyperproliferation: Roles of cell proliferation signal pathways

et al. 2016

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“…4 Dalam hal ini osteoklas distimulasi sitokinsitokin tertentu seperti IL-6. 10,11,20 Kadar IL-6 pada kolesteatoma subjek penelitian Pada analisis sampel kolesteatoma didapatkan adanya IL-6. Literatur menyebutkan bahwa perimatriks maupun matriks kolesteatoma dapat menghasilkan IL-6.5,8 TNF-α, IL-1 dan IL-6 didapatkan pada kolesteatoma dalam konsentrasi tinggi.…”

Section: Distribusi Derajat Kerusakan Tulang Pendengaran Pada Subjek Penelitianunclassified

Hubungan kadar Interleukin-6 kolesteatoma dengan derajat kerusakan tulang pendengaran pasien otitis media supuratif kronis

Widyatama¹,

Handoko²,

Wahyudiono³

2015

Oto Rhino Laryn Indones

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Latar belakang: Kolesteatoma adalah lesi keratin non-neoplastik yang berhubungan dengan proliferasi sel epitel dengan karakteristik morfologi yang menyimpang. Otitis Media Supuratif Kronis (OMSK) yang disertai dengan adanya kolesteatoma dapat mengganggu keseimbangan antara pembentukan tulang dengan resorpsi tulang. Kolesteatoma dapat menghasilkan sitokin-sitokin seperti interleukin-6 (IL-6) yang berperan dalam proses destruksi tulang pendengaran. Tujuan: Mengetahui distribusi derajat kerusakan tulang pendengaran pada pasien OMSK dengan kolesteatoma, rerata kadar IL-6 pada kolesteatoma, dan adanya hubungan antara kadar IL-6 pada kolesteatoma dengan derajat kerusakan tulang pendengaran pada pasien OMSK dengan kolesteatoma. Metode: Penelitian ini melibatkan 6 pasien dengan OMSK dengan kolesteatoma yang dilakukan operasi mastoidektomi. Satu pasien menderita OMSK dengan kolesteatoma bilateral dan dilakukan operasi mastoidektomi pada kedua telinganya. Derajat kerusakan tulang pendengaran dinilai dengan menggunakan kriteria Saleh danMills, sedangkan kadar IL-6 pada kolesteatoma diukur dengan menggunakan instrumen ELISA. Hasil:Derajat kerusakan tulang pendengaran tertinggi yang ditemukan adalah derajat 3 (28,57%), sedangkan derajat kerusakan tulang pendengaran yang terbanyak adalah derajat 2 (42,86%). Kadar IL-6 pada kolesteatoma yang tertinggi adalah 2290 pg/mL, sedangkan rerata kadar IL-6 pada kolesteatoma adalah 1778,57±392,616 pg/mL. Kesimpulan: Kadar IL-6 pada kolesteatoma tidak berhubungan dengan derajat kerusakan tulang pendengaran pada pasien OMSK dengan kolesteatoma (p=0,885).Kata kunci: Kadar IL-6 kolesteatoma, derajat kerusakan tulang pendengaran, OMSK dengan koles-teatoma. ABSTRACTBackgrounds: Cholesteatoma is non neoplastic keratinized lesion related to epithelial cell proliferation with deviated morphologic characteristic. Chronic Suppurative Otitis Media (CSOM) with cholesteatoma may cause imbalance between bone formation and resorption. Cholesteatoma may produce cytokines such as interleukin-6 (IL-6) which has a role in ossicle destruction. Objectives: To evaluate the distribution of ossicle destruction degree in CSOM with cholesteatoma patients, mean of IL-6 level in cholesteatoma and the relationship between IL-6 level in cholesteatoma and ossicle destruction degree in CSOM with cholesteatoma patients. Methods: This study involved 6 CSOM with cholesteatoma patients who underwent mastoidectomy. One patient had bilateral CSOM with cholesteatoma and underwent mastoidectomy in both ears. Ossicle destruction degree was determined by using Saleh and Mills criterias whereas IL-6 level in cholesteatoma was measured by using ELISA kit. Results: The highest ossicle destruction degree was the third degree (28.57%), whereas the most common ossicle destruction degree was the second degree (42.86%). The highest IL-6 level in cholesteatoma was2290 pg/mL, whereas mean of IL-6 level in cholesteatoma was 1778.57 ± 392.616 pg/mL. Conclusions: IL-6 level in cholesteatoma didn’t have relationship with ossicle destruction degree in CSOM with cholesteatoma patients (p=0,885).Keywords: IL-6 level in cholesteatoma, ossicle destruction degree, CSOM with cholesteatoma.

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In vitro cholesteatoma growth and secretion of cytokines

Cited by 12 publications

References 15 publications

Comparison of changes in mitochondrial bioenergetics between keratinocytes in human external auditory canal skin and cholesteatomas from normoxia to hypoxia

Comparison of changes in mitochondrial bioenergetics between keratinocytes in human external auditory canal skin and cholesteatomas from normoxia to hypoxia

Acquired cholesteatoma epithelial hyperproliferation: Roles of cell proliferation signal pathways

Hubungan kadar Interleukin-6 kolesteatoma dengan derajat kerusakan tulang pendengaran pasien otitis media supuratif kronis

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