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Grape Seed Proanthocyanidin Inhibits Mucin Synthesis and Viral Replication by Suppression of AP-1 and NF-kappa B via p38 MAPKs/JNK Signaling Pathways in Respiratory Syncytial Virus-Infected A549 Cells

Authors
Lee, Jin-WooKim, Young IlIm, Chang-NimKim, Sung WanKim, Su JinMin, SeoyeonJoo, Yong HoonYim, Sung-VinChung, Namhyun
Issue Date
7-6월-2017
Publisher
AMER CHEMICAL SOC
Keywords
AS49 cells; mucin; grape seed proanthocyanidin; respiratory syncytial virus
Citation
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, v.65, no.22, pp.4472 - 4483
Indexed
SCIE
SCOPUS
Journal Title
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume
65
Number
22
Start Page
4472
End Page
4483
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/83154
DOI
10.1021/acs.jafc.7b00923
ISSN
0021-8561
Abstract
Airway epithelial cells are often infected by respiratory syncytial virus (RSV), one of the most common causes of asthma, bronchiolitis, chronic obstructive pulmonary disease, and pneumonia. During the infection process, excessive mucins instigate airway inflammation. However, the mechanism underlying RSV-induced airway hyper-responsiveness and inflammation is poorly understood. Furthermore, no reliable vaccines or drugs for antiviral therapy are available. In this study, the effect of the natural compound grape seed proanthocyanidin (GSP) on RSV-infected human airway epithelial cells A549 was evaluated. After pretreatment of the cells with or without exposure to RSV with 5-10 mu g GSP/mL, the expression of various mucins (MUC1, MUC2, MUCSAC, MUC5B, and MUC8) was evaluated by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting, as well as confocal microscopy. We found that GSP significantly decreased RSV-induced mucin synthesis at the mRNA and protein levels. In addition, GSP suppressed the RSV-induced signaling pathways, including extra cellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, together with nuclear factor kappa B (NF-kappa B) and activating protein-1 family members (c-Jun and c-Fos). Concomitantly, GSP inhibited the replication of RSV within A549 cells. Taken together, all our results suggest that GSP could be a potent therapeutic agent to suppress excessive mucus production and viral replication in RSV-induced airway inflammatory disorders.
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