@article{oai:showa.repo.nii.ac.jp:00000547,
 author = {TSUCHIYA, Yutaka and WAKABAYASHI, Aya and MATSUKURA, Satoshi and OSAKABE, Yuki and SEKIGUCHI, Ayaka and INOUE, Daisuke and KAKIUCHI, Yusuke and FUNAKI, Toshitaka and YAMAZAKI, Yohei and TAKAYASU, Hiromi and TATENO, Hidetsugu and KATO, Eisuke and HAYASHI, Makoto and ISHII, Gen and YAMAGUCHI, Fumihiro and KOKUBU, Fumio},
 issue = {2},
 journal = {The Showa University journal of medical sciences},
 month = {2016-06, 2019-07-26},
 note = {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.},
 pages = {101--111},
 title = {Tumor Necrosis Factor-alpha and Transforming Growth Factor-beta Synergistically Upregulate Endothelin-1 Expression in Human Bronchial Epithelial Cells BEAS-2B},
 volume = {28},
 year = {}
}