title: Caffeic acid regulates LPS-induced NF-κB activation through NIK/IKK and c-Src/ERK signaling pathways in endothelial cells.
abstract: The redox sensitive, proinflammatory nuclear transcription factor NF-κB plays a key role in inflammation. In a redox state disrupted by oxidative stress, pro-inflammatory genes are upregulated by the activation of NF-κB via diverse kinases. Thus, the search and characterization of new substances that modulate NF-κB are topics of considerable research interest. Caffeic acid is a component of garlic, some fruits, and coffee, and is widely used as a phenolic agent in beverages. In the present study, caffeic acid was examined with respect to the modulation of inflammatory NF-κB activation via the redox-related c-Src/ERK and NIK/IKK pathways via the reduction of oxidative stress. YPEN-1 cells (an endothelial cell line) were used to explore the molecular mechanism underlying the anti-inflammatory effect of caffeic acid by examining its modulation of NF-κB signaling pathway by LPS. Our results show that LPS-induced oxidative stress-related NF-κB activation upregulated pro-inflammatory COX-2, NF-κB targeting gene which were all inhibited effectively by caffeic acid. Our study shows that caffeic acid inhibits the activation of NF-κB via the c-Src/ERK and NIK/IKK signal transduction pathways. Our results indicate that antioxidative effect of caffeic acid and its restoration of redox balance are responsible for its anti-inflammatory action. Thus, the study provides new information regarding the anti-inflammatory properties of caffeic acid and the roles in the regulation of LPS-induced oxidative stress induces alterations in signal transduction pathways.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Geumjeong-gu, Busan, 609-735, Korea.
authors.forename: So Ra
authors.initials: SR
authors.lastname: Kim
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Jung
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: An
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000893:Anti-Inflammatory Agents; D002109:Caffeic Acids; D048049:Extracellular Signal-Regulated MAP Kinases; D051550:I-kappa B Kinase; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D019061:src-Family Kinases; D000097782:NF-kappaB-Inducing Kinase; C040048:caffeic acid