Verproside inhibits TNF-α-induced MUC5AC expression through suppression of the TNF-α/NF-κB pathway in human airway epithelial cells

Cytokine
Su Ui LeeSei-Ryang Oh

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)β, IκBα, and TGF-β-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; TNF...Continue Reading

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Citations

Apr 27, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ju-Hyun KimHye Suk Lee
Jun 5, 2018·American Journal of Respiratory and Critical Care Medicine·Xiaoyun WangCaroline A Owen
Jun 21, 2019·Current Medicinal Chemistry·Liu-Qiang ZhangYi-Ming Li
Jun 24, 2019·Allergy·Ilse M BoudewijnVictor Guryev
Sep 2, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Stephen J Gurczynski, Bethany B Moore
Oct 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jingyuan Li, Zuguang Ye
Feb 28, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Lucas Amaral-MachadoEryvaldo Sócrates T Egito
Aug 24, 2021·Journal of Asthma and Allergy·Xu ChenWenchun Xu

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