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

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.

Nanoparticle delivery of grape seed-derived proanthocyanidins to airway epithelial cells dampens oxidative stress and inflammation

“…Although other groups have shown that SLN are capable of delivering other natural anti-oxidant compounds [ 58 ], to the best of our knowledge our study is the first to show the delivery of proanthocyanidins by SLN to airway epithelial cells and fluorochrome-containing SLN to the lungs in vivo. Only a previous paper showed that GSE, at the concentrations up to 20 µg/ml, was not cytotoxic to pulmonary A549 epithelial cells and reduced mucin transcript and protein expression as well as various signaling pathways involved in inflammation [ 66 ].…”

Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice

“…It remains unknown of the precise pathogenetic mechanisms of RSV that causes disease. The main clinical expression of RSV infection is excessive inflammatory and tissue damage (Lee et al, 2017;Vázquez et al, 2019). The release of pro-inflammatory cytokines usually causes excessive inflammatory response, mainly including interleukin IL-1b, IL-6, tumor necrosis factor (TNF-a) (Sun et al, 2018), and other members of the IL-1 gene family, for example, IL-18, IL-33 (Han et al, 2017;Yaneisi et al, 2019), etc.…”

Proanthocyanidins against Oxidative Stress: From Molecular Mechanisms to Clinical Applications

“…Via blocking NF- κ B and MAPK pathways, PCs in turn inhibit the mRNA expression of proinflammatory cytokines like TNF- α and IL-1 β as well as the inflammatory prostaglandin products of COX-2 [ 89 , 90 ]. In addition, PCs can suppress the replication of respiratory syncytial virus (RSV) by blocking RSV-induced NF- κ B, p38 MAPK/JNK, AP-1, and ERK activities [ 91 ].…”