Pretreatment with a grape seed proanthocyanidin extract downregulates proinflammatory cytokine expression in airway epithelial cells infected with respiratory syncytial virus

Kim,Su  Jin; Lee,Jin‑Woo; Eun,Young‑Gyu; Lee,Kun  Hee; Yeo,Seung  Gun; Kim,Sung  Wan

doi:10.3892/mmr.2019.9967

Pretreatment with a grape seed proanthocyanidin extract downregulates proinflammatory cytokine expression in airway epithelial cells infected with respiratory syncytial virus

Authors:
- Su Jin Kim
- Jin‑Woo Lee
- Young‑Gyu Eun
- Kun Hee Lee
- Seung Gun Yeo
- Sung Wan Kim
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Affiliations: Department of Otorhinolaryngology, Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, Republic of Korea, College of Life Sciences & Biotechnology, Korea University, Seoul 02841, Republic of Korea, Department of Otorhinolaryngology‑Head and Neck Surgery, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea
Published online on: February 19, 2019 https://doi.org/10.3892/mmr.2019.9967
Pages: 3330-3336

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Abstract

Respiratory syncytial virus (RSV) infections are associated with significant morbidity and mortality. Inflammation is mediated by cytokine secretion from RSV‑infected airway epithelial cells. Grape seed proanthocyanidin extract (GSPE) exhibits potent antioxidant capacity, as well as anti‑bacterial, anti‑viral, anti‑carcinogenic, anti‑inflammatory and anti‑allergic actions. However, few studies have explored the anti‑inflammatory effects of GSPE on airway epithelial cells infected with RSV. Airway epithelial A549 cells were pretreated with GSPE and its effects on cytokine production during RSV infection were investigated. A549 cells were infected with RSV, with or without GSPE pretreatment, and cultured for 24, 48 and 72 h. The expression of interleukin (IL)‑1β, IL‑6 and IL‑8, were measured by reverse transcription‑quantitative polymerase chain reaction, ELISA and western blotting. RSV infection induced significant increases in proinflammatory cytokine expression. However, GSPE pretreatment decreased the mRNA and protein expression levels of IL‑1ß, IL‑6 and IL‑8. GSPE regulated the immune response by reducing the RSV‑induced transcription of proinflammatory cytokines in airway epithelial cells, suggesting that GSPE helps to prevent RSV‑induced airway disease.

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1	Bont L, Checchia PA, Fauroux B, Figueras-Aloy J, Manzoni P, Paes B, Simões EA and Carbonell-Estrany X: Defining the epidemiology and burden of severe respiratory syncytial virus infection among infants and children in Western countries. Infect Dis Ther. 5:271–298. 2016. View Article : Google Scholar : PubMed/NCBI
2	Garofalo RP, Kolli D and Casola A: Respiratory syncytial virus infection: Mechanisms of redox control and novel therapeutic opportunities. Antioxid Redox Signal. 18:186–217. 2013. View Article : Google Scholar : PubMed/NCBI
3	Smith PK, Wang SZ, Dowling KD and Forsyth KD: Leucocyte populations in respiratory syncytial virus-induced bronchiolitis. J Paediatr Child Health. 37:146–151. 2001. View Article : Google Scholar : PubMed/NCBI
4	Abu-Harb M, Bell F, Finn A, Rao WH, Nixon L, Shale D and Everard ML: IL-8 and neutrophil elastase levels in the respiratory tract of infants with RSV bronchiolitis. Eur Respir J. 14:139–143. 1999. View Article : Google Scholar : PubMed/NCBI
5	Jones A, Qui JM, Bataki E, Elphick H, Ritson S, Evans GS and Everard ML: Neutrophil survival is prolonged in the airways of healthy infants and infants with RSV bronchiolitis. Eur Respir J. 20:651–657. 2002. View Article : Google Scholar : PubMed/NCBI
6	Borchers AT, Chang C, Gershwin ME and Gershwin LJ: Respiratory syncytial virus-a comprehensive review. Clin Rev Allergy Immunol. 45:331–379. 2013. View Article : Google Scholar : PubMed/NCBI
7	Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, Joshi SS and Pruess HG: Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology. 148:187–197. 2000. View Article : Google Scholar : PubMed/NCBI
8	Bagchi D, Sen CK, Ray SD, Das DK, Bagchi M, Preuss HG and Vinson JA: Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat Res. 523:87–97. 2003. View Article : Google Scholar : PubMed/NCBI
9	Akhtar S, Meeran SM, Katiyar N and Katiyar SK: Grape seed proanthocyanidins inhibit the growth of human non-small cell lung cancer xenografts by targeting insulin-like growth factor binding protein-3, tumor cell proliferation, and angiogenic factors. Clin Cancer Res. 15:821–831. 2009. View Article : Google Scholar : PubMed/NCBI
10	Bagchi D, Swaroop A, Preuss HG and Bagchi M: Free radical scavenging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: An overview. Mutat Res. 768:69–73. 2014. View Article : Google Scholar : PubMed/NCBI
11	Chacón MR, Ceperuelo-Mallafré V, Maymó-Masip E, Mateo-Sanz JM, Arola L, Guitiérrez C, Fernandez-Real JM, Ardèvol A, Simón I and Vendrell J: Grape-seed procyanidins modulate inflammation on human differentiated adipocytes in vitro. Cytokine. 47:137–142. 2009. View Article : Google Scholar : PubMed/NCBI
12	Gabetta B, Fuzzati N, Griffini A, Lolla E, Pace R, Ruffilli T and Peterlongo F: Characterization of proanthocyanidins from grape seeds. Fitoterapia. 71:162–175. 2000. View Article : Google Scholar : PubMed/NCBI
13	Dakhama A, Park JW, Taube C, Joetham A, Balhorn A, Miyahara N, Takeda K and Gelfand EW: The enhancement or prevention of airway hyperresponsiveness during reinfection with respiratory syncytial virus is critically dependent on the age at first infection and IL-13 production. J Immunol. 175:1876–1883. 2005. View Article : Google Scholar : PubMed/NCBI
14	LeVine AM, Elliott J, Whitsett JA, Srikiatkhachorn A, Crouch E, DeSilva N and Korfhagen T: Surfactant protein-d enhances phagocytosis and pulmonary clearance of respiratory syncytial virus. Am J Respir Cell Mol Biol. 31:193–199. 2004. View Article : Google Scholar : PubMed/NCBI
15	McKimm-Breschkin JL: A simplified plaque assay for respiratory syncytial virus-direct visualization of plaques without immunostaining. J Virol Methods. 120:113–117. 2004. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Heidema J, Lukens MV, van Maren WW, van Dijk ME, Otten HG, van Vught AJ, van der Werff DB, van Gestel SJ, Semple MG, Smyth RL, et al: CD8⁺ T cell responses in bronchoalveolar lavage fluid and peripheral blood mononuclear cells of infants with severe primary respiratory syncytial virus infections. J Immunol. 179:8410–8417. 2007. View Article : Google Scholar : PubMed/NCBI
18	Russell CD, Unger SA, Walton M and Schwarze J: The human immune response to respiratory syncytial virus infection. Clin Microbiol Rev. 30:481–502. 2017. View Article : Google Scholar : PubMed/NCBI
19	Ugonna K, Douros K, Bingle CD and Everard ML: Cytokine responses in primary and secondary respiratory syncytial virus infections. Pediatr Res. 79:946–950. 2016. View Article : Google Scholar : PubMed/NCBI
20	Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, Walsh EE, Freeman MW, Golenbock DT, Anderson LJ and Finberg RW: Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 1:398–401. 2000. View Article : Google Scholar : PubMed/NCBI
21	Polack FP, Irusta PM, Hoffman SJ, Schiatti MP, Melendi GA, Delgado MF, Laham FR, Thumar B, Hendry RM, Melero JA, et al: The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin. Proc Natl Acad Sci USA. 102:8996–9001. 2005. View Article : Google Scholar : PubMed/NCBI
22	Henriquez KM, Hayney MS, Xie Y, Zhang Z and Barrett B: Association of interleukin-8 and neutrophils with nasal symptom severity during acute respiratory infection. J Med Virol. 87:330–337. 2015. View Article : Google Scholar : PubMed/NCBI
23	Terra X, Valls J, Vitrac X, Mérrillon JM, Arola L, Ardèvol A, Bladé C, Fernandez-Larrea J, Pujadas G, Salvadó J and Blay M: Grape-seed procyanidins act as antiinflammatory agents in endotoxin-stimulated RAW 264.7 macrophages by inhibiting NFkB signaling pathway. J Agric Food Chem. 55:4357–4365. 2007. View Article : Google Scholar : PubMed/NCBI
24	Terra X, Montagut G, Bustos M, Llopiz N, Ardèvol A, Bladé C, Fernández-Larrea J, Pujadas G, Salvadó J, Arola L and Blay M: Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J Nutr Biochem. 20:210–218. 2009. View Article : Google Scholar : PubMed/NCBI
25	Kim H, Kim JY, Song HS, Park KU, Mun KC and Ha E: Grape seed proanthocyanidin extract inhibits interleukin-17-induced interleukin-6 production via MAPK pathway in human pulmonary epithelial cells. Naunyn Schmiedebergs Arch Pharmacol. 383:555–562. 2011. View Article : Google Scholar : PubMed/NCBI
26	Sakurai T, Kitadate K, Nishioka H, Fujii H, Kizaki T, Kondoh Y, Izawa T, Ishida H, Radák Z and Ohno H: Oligomerized grape seed polyphenols attenuate inflammatory changes due to antioxidative properties in coculture of adipocytes and macrophages. J Nutr Biochem. 21:47–54. 2010. View Article : Google Scholar : PubMed/NCBI
27	Castro SM, Guerrero-Plata A, Suarez-Real G, Adegboyega PA, Colasurdo GN, Khan AM, Garofalo RP and Casola A: Antioxidant treatment ameliorates respiratory syncytial virus-induced disease and lung inflammation. Am J Respir Crit Care Med. 174:1361–1369. 2006. View Article : Google Scholar : PubMed/NCBI
28	Bellik Y, Boukraâ L, Alzahrani HA, Bakhotmah BA, Abdellah F, Hammoudi SM and Iguer-Ouada M: Molecular mechanism underlying anti-inflammatory and anti-allergic activities of phytochemicals: An update. Molecules. 18:322–353. 2012. View Article : Google Scholar : PubMed/NCBI