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Verproside inhibits TNF-α-induced MUC5AC expression through suppression of the TNF-α/NF-κB pathway in human airway epithelial cells.
Lee, Su Ui; Sung, Min Hee; Ryu, Hyung Won; Lee, Jinhyuk; Kim, Hui-Seong; In, Hyun Ju; Ahn, Kyung-Seop; Lee, Hyun-Jun; Lee, Hyeong-Kyu; Shin, Dae-Hee; Lee, Yongnam; Hong, Sung-Tae; Oh, Sei-Ryang.
Afiliação
  • Lee SU; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 363-883, Republic of Korea.
  • Sung MH; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 363-883, Republic of Korea.
  • Ryu HW; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 363-883, Republic of Korea.
  • Lee J; Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
  • Kim HS; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 363-883, Republic of Korea.
  • In HJ; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 363-883, Republic of Korea.
  • Ahn KS; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 363-883, Republic of Korea.
  • Lee HJ; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 363-883, Republic of Korea.
  • Lee HK; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 363-883, Republic of Korea.
  • Shin DH; Central R&D Institute, Yungjin Pharm. Co., Ltd., Suwon 443-270, Republic of Korea.
  • Lee Y; Central R&D Institute, Yungjin Pharm. Co., Ltd., Suwon 443-270, Republic of Korea.
  • Hong ST; Department of Biological Sciences, Korea Advanced Institute of Science & Technology, Guseong-Dong, Yusong-Gu, Daejeon 305-701, Republic of Korea. Electronic address: mogwai@kaist.ac.kr.
  • Oh SR; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 363-883, Republic of Korea. Electronic address: seiryang@kribb.re.kr.
Cytokine ; 77: 168-75, 2016 Jan.
Article em En | MEDLINE | ID: mdl-26318254
ABSTRACT
Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of MUC5AC, are significant risk factors in asthma and chronic obstructive pulmonary disease (COPD) patients. Previously, we reported that verproside, a catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum var. subintegrum, is a potent anti-asthmatic candidate drug in vivo. However, the molecular mechanisms underlying the pharmacological actions of verproside remain unknown. Here, we found that verproside significantly reduces the expression levels of tumor necrosis factor alpha (TNF-α)-induced MUC5AC mRNA and protein by inhibiting both nuclear factor kappa B (NF-κB) transcriptional activity and the phosphorylation of its upstream effectors such as IκB kinase (IKK)ß, IκBα, and TGF-ß-activated kinase 1 (TAK1) in NCI-H292 cells. Moreover, verproside attenuated TNF-α-induced MUC5AC transcription more effectively when combined with an IKK (BAY11-7082) or a TAK1 (5z-7-oxozeaenol) inhibitor than when administered alone. Importantly, we demonstrated that verproside negatively modulates the formation of the TNF-α-receptor (TNFR) 1 signaling complex [TNF-RSC; TNFR1-recruited TNFR1-associated death domain protein (TRADD), TNFR-associated factor 2 (TRAF2), receptor-interacting protein kinase 1 (RIP1), and TAK1], the most upstream signaling factor of NF-κB signaling. In silico molecular docking studies show that verproside binds between TRADD and TRAF2 subunits. Altogether, these results suggest that verproside could be a good therapeutic candidate for treatment of inflammatory airway diseases such as asthma and COPD by blocking the TNF-α/NF-κB signaling pathway.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / NF-kappa B / Fator de Necrose Tumoral alfa / Células Epiteliais / Mucina-5AC / Glucosídeos Iridoides Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / NF-kappa B / Fator de Necrose Tumoral alfa / Células Epiteliais / Mucina-5AC / Glucosídeos Iridoides Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article