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

Jin Woo Lee, Young Il Kim, Chang Nim Im, Sung Wan Kim, Su Jin Kim, Seoyeon Min, Yong Hoon Joo, Sung Vin Yim, Namhyun Chung

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 μg GSP/mL, the expression of various mucins (MUC1, MUC2, MUC5AC, 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 extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, together with nuclear factor kappa B (NF-κB) 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.

Original languageEnglish
Pages (from-to)4472-4483
Number of pages12
JournalJournal of Agricultural and Food Chemistry
Volume65
Issue number22
DOIs
Publication statusPublished - 2017 Jun 7

Fingerprint

grape seeds
Respiratory Syncytial Viruses
MAP Kinase Signaling System
NF-kappa B
mucins
Transcription Factor AP-1
p38 Mitogen-Activated Protein Kinases
Mucins
virus replication
proanthocyanidins
Viruses
mitogen-activated protein kinase
viruses
synthesis
cells
Respiratory Hypersensitivity
epithelial cells
inflammation
Human respiratory syncytial virus
Epithelial Cells

Keywords

  • A549 cells
  • grape seed proanthocyanidin
  • mucin
  • respiratory syncytial virus

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Cite this

Grape Seed Proanthocyanidin Inhibits Mucin Synthesis and Viral Replication by Suppression of AP-1 and NF-κB via p38 MAPKs/JNK Signaling Pathways in Respiratory Syncytial Virus-Infected A549 Cells. / Lee, Jin Woo; Kim, Young Il; Im, Chang Nim; Kim, Sung Wan; Kim, Su Jin; Min, Seoyeon; Joo, Yong Hoon; Yim, Sung Vin; Chung, Namhyun.

In: Journal of Agricultural and Food Chemistry, Vol. 65, No. 22, 07.06.2017, p. 4472-4483.

Research output: Contribution to journalArticle

Lee, Jin Woo ; Kim, Young Il ; Im, Chang Nim ; Kim, Sung Wan ; Kim, Su Jin ; Min, Seoyeon ; Joo, Yong Hoon ; Yim, Sung Vin ; Chung, Namhyun. / Grape Seed Proanthocyanidin Inhibits Mucin Synthesis and Viral Replication by Suppression of AP-1 and NF-κB via p38 MAPKs/JNK Signaling Pathways in Respiratory Syncytial Virus-Infected A549 Cells. In: Journal of Agricultural and Food Chemistry. 2017 ; Vol. 65, No. 22. pp. 4472-4483.
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AU - Lee, Jin Woo

AU - Kim, Young Il

AU - Im, Chang Nim

AU - Kim, Sung Wan

AU - Kim, Su Jin

AU - Min, Seoyeon

AU - Joo, Yong Hoon

AU - Yim, Sung Vin

AU - Chung, Namhyun

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AB - 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 μg GSP/mL, the expression of various mucins (MUC1, MUC2, MUC5AC, 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 extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, together with nuclear factor kappa B (NF-κB) 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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