| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Zdroj: |
The Showa University journal of medical sciences. 28(2):101-111 |
| ISSN: |
0915-6380 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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