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Oleanolic Acid Acetate Exerts Anti-Inflammatory Activity via IKKα/ß Suppression in TLR3-Mediated NF-κB Activation.
Lim, Hyung Jin; Jang, Hyun-Jae; Kim, Mi Hwa; Lee, Soyoung; Lee, Seung Woong; Lee, Seung-Jae; Rho, Mun-Chual.
Afiliação
  • Lim HJ; Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
  • Jang HJ; Department of Bioactive Material Sciences, Chonbuk National University, Jeonju-si 54896, Korea.
  • Kim MH; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Cheongju-si 28116, Korea.
  • Lee S; Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
  • Lee SW; Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
  • Lee SJ; Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
  • Rho MC; Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
Molecules ; 24(21)2019 Nov 05.
Article em En | MEDLINE | ID: mdl-31694243
Oleanolic acid acetate (OAA), a major triterpenoid compound of Vigna angularis (azuki bean, V. angularis), has been shown to downregulate inflammatory responses in macrophages. Here, we show the molecular basis for the effect of OAA on Toll-like receptor (TLR) downstream signaling. OAA treatment significantly inhibited the secretion of embryonic alkaline phosphatase (SEAP) induced by polyinosinic acid (poly(I), TLR3 ligand) in a dose-dependent manner and without cytotoxicity in THP1-XBlue cells. In addition, OAA downregulated the gene expression of poly(I) induced pro-inflammatory cytokines and chemokines genes such as MCP-1, IL-1ß, IL-8, VCAM-1 and ICAM-1. Furthermore, we found that the inhibition activity of OAA was accompanied by decreased activation of not only nuclear factor-kappa B (NF-κB) signaling but also mitogen-activated protein kinase (MAPK) signaling upon stimulation with the TLR3 agonist. Interestingly, the interaction of OAA with IκB kinase α/ß (IKKα/ß) strongly attenuated the production of certain proteins and inflammatory cytokines in the TLR3 signaling pathway, such as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBα), extracellular regulated kinases (ERK), and p38, in an in vitro model. The action of OAA was regulated by TLR3, demonstrating that TLR3 plays a critical role in mediating the physiologically-relevant anti-inflammatory action of OAA and that the interaction with IKKα/ß is modulated through TLR3. These results reveal new insight into the understanding of the regulatory mechanisms of the downstream TLR3 signaling pathway and consequent inflammatory responses that are involved in the development and progression of inflammatory diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácido Oleanólico / NF-kappa B / Quinase I-kappa B / Receptor 3 Toll-Like / Inflamação / Acetatos / Anti-Inflamatórios Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácido Oleanólico / NF-kappa B / Quinase I-kappa B / Receptor 3 Toll-Like / Inflamação / Acetatos / Anti-Inflamatórios Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2019 Tipo de documento: Article