Abstract
This study was aimed to investigate the effect of grape seed proanthocyanidin extract (GSPE) on interleukin-17 (IL-17)-induced interleukin-6 (IL-6) production in A549 human pulmonary epithelial cells. Cells were treated with IL-17 (10 ng/ml) or GSPE (50 μg/ml), or both. The effects of GSPE on cell viability and apoptosis were evaluated. The mRNA and protein levels of IL-6 were determined by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Expressions of inhibitory factor κB-α (IκB-α) and ERK 1/2, p38, and JNK mitogen-activated protein kinase (MAPK) were examined by Western blot analysis. GSPE significantly inhibited both GSPE treatment only and IL-17-induced mRNA expressions and protein productions of IL-6 in pulmonary epithelial cells (p < 0.01). GSPE decreased the IL-17-induced phosphorylation of IκB-α. The IL-17 stimulated ERK 1/2, p38, and JNK MAPK activities and GSPE decreased IL-17-stimulated ERK 1/2, p38, and JNK MAPK activities. GSPE also attenuated TNF-α and IL-1β-induced IL-6 productions (p < 0.05). Our results show that GSPE may inhibit IL-17-stimulated IL-6 productions in human pulmonary epithelial cells by inhibiting MAPK and nuclear factor-κB-mediated signaling pathway.
Similar content being viewed by others
References
Akhtar S, Meeran SM, Katiyar N, Katiyar SK (2009) 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
Awane M, Andres PG, Li DJ, Reinecker HC (1999) NF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and IL-1 beta-induced chemokine promoter activation in intestinal epithelial cells. J Immunol 162:5337–5344
Bagchi D, Das DK, Engelman RM, Prasad MR, Subramanian R (1990) Polymorphonuclear leucocytes as potential source of free radicals in the ischaemic-reperfused myocardium. Eur Heart J 11:800–813
Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ (1997) Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol 95:179–189
Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA et al (2000) Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 148:187–197
Bagchi D, Sen CK, Ray SD, Das DK, Bagchi M, Preuss HG et al (2003) Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat Res 523–524:87–97
Chacon MR, Ceperuelo-Mallafre V, Maymo-Masip E, Mateo-Sanz JM, Arola L, Guitierrez C et al (2009) Grape-seed procyanidins modulate inflammation on human differentiated adipocytes in vitro. Cytokine 47:137–142
Cho ML, Heo YJ, Park MK, Oh HJ, Park JS, Woo YJ et al (2009) Grape seed proanthocyanidin extract (GSPE) attenuates collagen-induced arthritis. Immunol Lett 124:102–110
Crowe CR, Chen K, Pociask DA, Alcorn JF, Krivich C, Enelow RI et al (2009) Critical role of IL-17RA in immunopathology of influenza infection. J Immunol 183:5301–5310
Hacievliyagil SS, Gunen H, Mutlu LC, Karabulut AB, Temel I (2006) Association between cytokines in induced sputum and severity of chronic obstructive pulmonary disease. Respir Med 100:846–854
Halliwell B, Gutteridge JM, Cross CE (1992) Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med 119:598–620
Hashimoto T, Akiyama K, Kobayashi N, Mori A (2005) Comparison of IL-17 production by helper T cells among atopic and nonatopic asthmatics and control subjects. Int Arch Allergy Immunol 137(Suppl 1):51–54
Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producting CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132
Johnson-Varghese L, Brodsky N, Bhandari V (2004) Effect of antioxidants on apoptosis and cytokine release in fetal rat Type II pneumocytes exposed to hyperoxia and nitric oxide. Cytokine 28:10–16
Kawaguchi M, Kokubu F, Kuga H, Matsukura S, Hoshino H, Ieki K et al (2001) Modulation of bronchial epithelial cells by IL-17. J Allergy Clin Immunol 108:804–809
Kolls JK, Kanaly ST, Ramsay AJ (2003) Interleukin-17: an emerging role in lung inflammation. Am J Respir Cell Mol Biol 28:9–11
Laan M, Cui ZH, Hoshino H, Lotvall J, Sjostrand M, Gruenert DC et al (1999) Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways. J Immunol 162:2347–2352
Laan M, Lotvall J, Chung KF, Linden A (2001) IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role of mitogen-activated protein (MAP) kinases. Br J Pharmacol 133:200–206
Li H, Witte K, August M, Brausch I, Godtel-Armbrust U, Habermeier A et al (2006) Reversal of endothelial nitric oxide synthase uncoupling and up-regulation of endothelial nitric oxide synthase expression lowers blood pressure in hypertensive rats. J Am Coll Cardiol 47:2536–2544
Linden A (2001) Role of interleukin-17 and the neutrophil in asthma. Int Arch Allergy Immunol 126:179–184
Linden A, Hoshino H, Laan M (2000) Airway neutrophis and interleukin-17. Eur Respir J 15:973–977
Linden A, Laan M, Anderson GP (2005) Neutrophils, interleukin-17A and lung disease. Eur Respir J 25:159–172
Lippi G, Franchini M, Favaloro EJ, Targher G (2010) Moderate red wine consumption and cardiovascular disease risk: beyond the “French paradox”. Semin Thromb Hemost 36:59–70
Liu HT, He JL, Li WM, Yang Z, Wang YX, Yin J et al (2010) Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways. Inflamm Res 59:451–461
Ma L, Gao HQ, Li BY, Ma YB, You BA, Zhang FL (2007) Grape seed proanthocyanidin extracts inhibit vascular cell adhesion molecule expression induced by advanced glycation end products through activation of peroxisome proliferators-activated receptor gamma. J Cardiovasc Pharmacol 49:293–298
Ma X, Reynolds SL, Baker BJ, Li X, Benveniste EN, Qin H (2010) IL-17 enhancement of the IL-6 signaling cascade in astrocytes. J Immunol 184:4898–4906
Marini M, Vittori E, Hollemborg J, Mattoli S (1992) Expression of the potent inflammatory cytokines, granulocyte-macrophage-colony-stimulating factor and interleukin-6 and interleukin-8, in bronchial epithelial cells of patients with asthma. J Allergy Clin Immunol 89:1001–1009
Miljkovic D, Cvetkovic I, Vuckovic O, Stosic-Grujicic S, Mostarica Stojkovic M, Trajkovic V (2003) The role of interleukin-17 in inducible nitric oxide synthase-mediated nitric oxide production in endothelial cells. Cell Mol Life Sci 60:518–525
Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Page N et al (2001) IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 108:430–438
Ning W, Choi AM, Li C (2005) Carbon monoxide inhibits IL-17-induced IL-6 production through the MAPK pathway in human pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 289:L268–L273
Prause O, Laan M, Lotvall J, Linden A (2003) Pharmacological modulation of interleukin-17-induced GCP-2-, GRO-alpha- and interleukin-8 release in human bronchial epithelial cells. Eur J Pharmacol 462:193–198
Renaud S, de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339:1523–1526
Roussel L, Houle F, Chan C, Yao Y, Berube J, Olivenstein R et al (2010) IL-17 promotes p38 MAPK-dependent endothelial activation enhancing neutrophil recruitment to sites of inflammation. J Immunol 184:4531–4537
Sen CK, Bagchi D (2001) Regulation of inducible adhesion molecule expression in human endothelial cells by grape seed proanthocyanidin extract. Mol Cell Biochem 216:1–7
Shalom-Barak T, Quach J, Lotz M (1998) Interleukin-17-induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF-kappaB. J Biol Chem 273:27467–27473
Sharma SD, Katiyar SK (2010) Dietary grape seed proanthocyanidins inhibit UVB-induced cyclooxygenase-2 expression and other inflammatory mediators in UVB-exposed skin and skin tumors of SKH-1 hairless mice. Pharm Res 27:1092–1102
Sorescu D, Weiss D, Lassegue B, Clempus RE, Szocs K et al (2002) Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation 105:1429–1435
Stankiewicz W, Dabrowski MP, Chcialowski A, Plusa T (2002) Cellular and cytokine immunoregulation in patients with chronic obstructive pulmonary disease and bronchial asthma. Mediat Inflamm 11:307–312
Starnes T, Robertson MJ, Sledge G, Kelich S, Nakshatri H, Broxmeyer HE et al (2001) Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. J Immunol 167:4137–4140
Terra X, Montagut G, Bustos M, Llopiz N, Ardevol A, Blade C et al (2009) Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J Nutr Biochem 20:210–218
Tillie-Leblond I, Pugin J, Marquette CH, Lamblin C, Saulnier F, Brichet A et al (1999) Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmaticus. Am J Respir Crit Care Med 159:487–494
Vanaudenaerde BM, Wuyts WA, Dupont LJ, Van Raemdonck DE, Demedts MM, Verleden GM (2003) Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle cells in vitro: a potential role for interleukin-17 and airway smooth muscle cells in bronchiolitis obliterans syndrome. J Heart Lung Transplant 22:1280–1283
Wong CK, Ho CY, Li EK, Lam CW (2000) Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus 9:589–593
Wong CK, Wang CB, Ip WK, Tian YP, Lam CW (2005) Role of p38 MAPK and NF-kB for chemokine release in coculture of human eosinophils and bronchial epithelial cells. Clin Exp Immunol 139:90–100
Wuyts WA, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE, Demedts MG, Verleden GM (2005) Interleukin-17—induced interleukin-8 release in human airway smooth muscle cells: role for mitogen-activated kinases and nuclear factor-kappaB. J Heart Lung Transplant 24:875–881
Yagi Y, Andoh A, Inatomi O, Tsujikawa T, Fujiyama Y (2007) Inflammatory responses induced by interleukin-17 family members in human colonic subepithelial myofibroblasts. J Gastroenterol 42:746–753
Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, Schwarzenberger P, Oliver P, Huang W, Zhang P, Zhang J, Shellito JE, Bagby GJ, Nelson S, Charrier K, Peschon JJ, Kolls JK (2001) Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med 194:519–527
Acknowledgments
The present research has been conducted by attached research institute research grant of Keimyung University in 2007.
Author information
Authors and Affiliations
Corresponding author
Additional information
Hyeongseok Kim and Jin Young Kim contributed equally to this work.
Rights and permissions
About this article
Cite this article
Kim, H., Kim, J.Y., Song, H.S. et al. Grape seed proanthocyanidin extract inhibits interleukin-17-induced interleukin-6 production via MAPK pathway in human pulmonary epithelial cells. Naunyn-Schmiedeberg's Arch Pharmacol 383, 555–562 (2011). https://doi.org/10.1007/s00210-011-0633-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-011-0633-y