PMID- 31694243
OWN - NLM
STAT- MEDLINE
DCOM- 20200325
LR  - 20200325
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 24
IP  - 21
DP  - 2019 Nov 5
TI  - Oleanolic Acid Acetate Exerts Anti-Inflammatory Activity via IKKalpha/beta Suppression 
      in TLR3-Mediated NF-kappaB Activation.
LID - 10.3390/molecules24214002 [doi]
LID - 4002
AB  - 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-1beta, 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-kappaB) signaling but also mitogen-activated protein 
      kinase (MAPK) signaling upon stimulation with the TLR3 agonist. Interestingly, 
      the interaction of OAA with IkappaB kinase alpha/beta (IKKalpha/beta) 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 (IkBalpha), 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 IKKalpha/beta 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.
FAU - Lim, Hyung Jin
AU  - Lim HJ
AD  - Immunoregulatory Material Research Center, Korea Research Institute of Bioscience 
      and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
AD  - Department of Bioactive Material Sciences, Chonbuk National University, Jeonju-si 
      54896, Korea.
FAU - Jang, Hyun-Jae
AU  - Jang HJ
AUID- ORCID: 0000-0002-4383-4465
AD  - Natural Medicine Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, 30 Yeongudanji-ro, Cheongju-si 28116, Korea.
FAU - Kim, Mi Hwa
AU  - Kim MH
AD  - Immunoregulatory Material Research Center, Korea Research Institute of Bioscience 
      and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
FAU - Lee, Soyoung
AU  - Lee S
AD  - Immunoregulatory Material Research Center, Korea Research Institute of Bioscience 
      and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
FAU - Lee, Seung Woong
AU  - Lee SW
AUID- ORCID: 0000-0003-1025-7363
AD  - Immunoregulatory Material Research Center, Korea Research Institute of Bioscience 
      and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
FAU - Lee, Seung-Jae
AU  - Lee SJ
AD  - Immunoregulatory Material Research Center, Korea Research Institute of Bioscience 
      and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
FAU - Rho, Mun-Chual
AU  - Rho MC
AD  - Immunoregulatory Material Research Center, Korea Research Institute of Bioscience 
      and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Korea.
LA  - eng
GR  - P0000811/Korea Institute for Advancement of Technology/
GR  - 2015K000281/Ministry of Science, ICT and Future Planning/
GR  - KGS9531911/Korea Research Institute of Bioscience and Biotechnology/
GR  - KGS1081911/Korea Research Institute of Bioscience and Biotechnology/
PT  - Journal Article
DEP - 20191105
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Acetates)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (TLR3 protein, human)
RN  - 0 (Toll-Like Receptor 3)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Acetates/*pharmacology
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Down-Regulation/drug effects
MH  - Gene Expression/drug effects
MH  - Humans
MH  - I-kappa B Kinase/*metabolism
MH  - Inflammation/*drug therapy/metabolism
MH  - Macrophages/drug effects/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/*metabolism
MH  - Oleanolic Acid/*pharmacology
MH  - Signal Transduction/drug effects
MH  - Toll-Like Receptor 3/*metabolism
PMC - PMC6866124
OTO - NOTNLM
OT  - IkappaB kinase alpha/beta
OT  - Vigna angularis
OT  - inflammatory cytokines
OT  - oleanolic acid acetate
OT  - toll-like receptors
COIS- The authors declare no conflicts of interest.
EDAT- 2019/11/07 06:00
MHDA- 2020/03/26 06:00
PMCR- 2019/11/05
CRDT- 2019/11/08 06:00
PHST- 2019/10/02 00:00 [received]
PHST- 2019/11/04 00:00 [revised]
PHST- 2019/11/04 00:00 [accepted]
PHST- 2019/11/08 06:00 [entrez]
PHST- 2019/11/07 06:00 [pubmed]
PHST- 2020/03/26 06:00 [medline]
PHST- 2019/11/05 00:00 [pmc-release]
AID - molecules24214002 [pii]
AID - molecules-24-04002 [pii]
AID - 10.3390/molecules24214002 [doi]
PST - epublish
SO  - Molecules. 2019 Nov 5;24(21):4002. doi: 10.3390/molecules24214002.