| Item type |
学内発行雑誌 / Departmental Bulletin Paper(1) |
| 公開日 |
2017-02-14 |
| タイトル |
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タイトル |
Tumor Necrosis Factor-alpha and Transforming Growth Factor-beta Synergistically Upregulate Endothelin-1 Expression in Human Bronchial Epithelial Cells BEAS-2B |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ |
departmental bulletin paper |
| 著者 |
TSUCHIYA, Yutaka
WAKABAYASHI, Aya
MATSUKURA, Satoshi
OSAKABE, Yuki
SEKIGUCHI, Ayaka
INOUE, Daisuke
KAKIUCHI, Yusuke
FUNAKI, Toshitaka
YAMAZAKI, Yohei
TAKAYASU, Hiromi
TATENO, Hidetsugu
KATO, Eisuke
HAYASHI, Makoto
ISHII, Gen
YAMAGUCHI, Fumihiro
KOKUBU, Fumio
|
| 書誌情報 |
The Showa University journal of medical sciences
巻 28,
号 2,
p. 101-111,
発行日 2016-06
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| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Endothelin-1 is a peptide with many functions including bronchoconstriction and the stimulation of fibroblasts, and myofibroblasts, and airway smooth muscle cell proliferation. These functions are related to airway remodeling and endothelin-1 is known to be upregulated in the epithelium of patients with severe asthma. We thus sought to elucidate the mechanisms underlying endothelin-1 expression in bronchial epithelial cells in vitro. The human bronchial epithelial cell line BEAS-2B was grown in culture and then treated with tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), interleukin-13 (IL-13), and transforming growth factor-beta (TGF-β). Expression of endothelin-1 mRNA and protein was quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. We also repressed expression of the key transcription factor in the pathogenesis of severe asthma, nuclear factor-kappa B (NF-κB), using small interfering RNA (siRNA). TNF-α and TGF-β significantly increased the release of endothelin-1 protein into the culture medium of BEAS-2B cells at 24 h after treatment compared to untreated cells; however, the Th2 cytokines, IL-4 and IL-13, had no effect. Endothelin-1 mRNA expression was also upregulated by TNF-α and TGF-β with a peak time point at 4 h after stimulation. Finally, the combination of TNF-α and TGF-β synergistically increased both endothelin-1 protein secretion and mRNA expression, and this upregulation was significantly suppressed in cells transfected with siRNA to repress NF-κB expression. TNF-α and TGF-β synergistically upregulate the expression of endothelin-1 in human bronchial epithelial cells, possibly via the activity of NF-κB. Our findings thus suggest NF-κBa as a potential therapeutic target for the regulation of airway remodeling. |
| DOI |
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関連識別子 |
10.15369/sujms.28.101 |
| 出版者 |
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出版者 |
Showa University Society |
| ISSN |
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収録物識別子 |
0915-6380 |
| 著者版フラグ |
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出版タイプ |
VoR |
S28_101.pdf (443.3 kB)
