PMID- 32106625
OWN - NLM
STAT- MEDLINE
DCOM- 20201125
LR  - 20201125
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 5
DP  - 2020 Feb 25
TI  - Anti-Inflammatory and Anti-Oxidative Activity of Indole-3-Acetic Acid Involves 
      Induction of HO-1 and Neutralization of Free Radicals in RAW264.7 Cells.
LID - 10.3390/ijms21051579 [doi]
LID - 1579
AB  - The cellular and molecular mechanisms by which indole-3-acetic acid (IAA), a 
      tryptophan-derived metabolite from gut microbiota, attenuates inflammation and 
      oxidative stress has not been fully elucidated. The present study was to unearth 
      the protective effect and underlying mechanism of IAA against lipopolysaccharide 
      (LPS)-induced inflammatory response and free radical generation in RAW264.7 
      macrophages. IAA significantly ameliorated LPS-induced expression of 
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and monocyte chemoattractant 
      protein-1 (MCP-1) as well as generation of reactive oxidative species (ROS) and 
      nitric oxide (NO). LPS-triggered nuclear translocation of nuclear factor kappa B 
      (NF-kappaB) p65 was mitigated by IAA treatment. Further, an up-regulation of heme 
      oxygenase-1 (HO-1) was observed in IAA-treated cells in dose-dependent manner 
      under both normal and LPS-stimulated condition. Interference of HO-1 activity by 
      tin protoporphyrin IX (SnPP) impeded the alleviative effects of IAA on expression 
      of IL-1beta and IL-6 induced by LPS, whereas demonstrated no effect on its 
      suppression of ROS and NO production. This result suggests a HO-1-dependent 
      anti-inflammatory effect of IAA and its direct scavenging action on free 
      radicals. Treatment with CH-223191, a specific antagonist of aryl hydrocarbon 
      receptor (AhR), showed no significant effects on the beneficial role of IAA 
      against inflammation and free radical generation. In summary, our findings 
      indicate that IAA alleviates LPS-elicited inflammatory response and free radical 
      generation in RAW264.7 macrophages by induction of HO-1 and direct neutralization 
      of free radicals, a mechanism independent of AhR.
FAU - Ji, Yun
AU  - Ji Y
AUID- ORCID: 0000-0002-3483-0729
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of 
      Education, Beijing 100191, China.
FAU - Yin, Wenzhen
AU  - Yin W
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of 
      Education, Beijing 100191, China.
FAU - Liang, Yuan
AU  - Liang Y
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of 
      Education, Beijing 100191, China.
FAU - Sun, Lijun
AU  - Sun L
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of 
      Education, Beijing 100191, China.
FAU - Yin, Yue
AU  - Yin Y
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of 
      Education, Beijing 100191, China.
FAU - Zhang, Weizhen
AU  - Zhang W
AUID- ORCID: 0000-0001-8791-2798
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of 
      Education, Beijing 100191, China.
LA  - eng
GR  - 2017YFC0908900/the National Key R&D Program of China/
GR  - 2018M641113/the Projects funded by China Postdoctoral Science Foundation/
GR  - 81730020 and 81930015/the National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20200225
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Indoleacetic Acids)
RN  - 0 (Interleukins)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 6U1S09C61L (indoleacetic acid)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Antioxidants/*pharmacology
MH  - Cell Survival/drug effects
MH  - Chemokine CCL2/genetics/metabolism
MH  - Heme Oxygenase-1/*metabolism
MH  - Indoleacetic Acids/*pharmacology
MH  - Interleukins/genetics/metabolism
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - RAW 264.7 Cells
MH  - Reactive Oxygen Species/*metabolism
PMC - PMC7084870
OTO - NOTNLM
OT  - HO-1
OT  - LPS
OT  - free radical
OT  - indole-3-acetic acid
OT  - inflammation
OT  - macrophage
COIS- The authors declare no conflicts of interest.
EDAT- 2020/02/29 06:00
MHDA- 2020/11/26 06:00
PMCR- 2020/03/01
CRDT- 2020/02/29 06:00
PHST- 2020/02/15 00:00 [received]
PHST- 2020/02/22 00:00 [revised]
PHST- 2020/02/24 00:00 [accepted]
PHST- 2020/02/29 06:00 [entrez]
PHST- 2020/02/29 06:00 [pubmed]
PHST- 2020/11/26 06:00 [medline]
PHST- 2020/03/01 00:00 [pmc-release]
AID - ijms21051579 [pii]
AID - ijms-21-01579 [pii]
AID - 10.3390/ijms21051579 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Feb 25;21(5):1579. doi: 10.3390/ijms21051579.