title: Grape seed proanthocyanidin extract inhibits interleukin-17-induced interleukin-6 production via MAPK pathway in human pulmonary epithelial cells.
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.
authors.affiliation: Department of Biochemistry, Pain Research Center, School of Medicine, Keimyung University, Daegu 704-701, Republic of Korea.
authors.forename: Hyeongseok
authors.initials: H
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hong Suk
authors.initials: HS
authors.lastname: Song
authors.forename: Keon Uk
authors.initials: KU
authors.lastname: Park
authors.forename: Kyo-Chul
authors.initials: KC
authors.lastname: Mun
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Ha
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D056604:Grape Seed Extract / Q000494:pharmacology*; D006801:Humans; D020381:Interleukin-17 / Q000008:administration & dosage / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D056604:Grape Seed Extract; D020381:Interleukin-17; D015850:Interleukin-6; D016328:NF-kappa B; D044945:Proanthocyanidins; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases