PMID- 33831807
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20211214
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 96
DP  - 2021 Jul
TI  - Inonotsuoxide B regulates M1 to M2 macrophage polarization through 
      sirtuin-1/endoplasmic reticulum stress axis.
PG  - 107603
LID - S1567-5769(21)00239-3 [pii]
LID - 10.1016/j.intimp.2021.107603 [doi]
AB  - We explored the effect of tetracyclic triterpenoid inonotsuoxide B (IB) extracts 
      of Inonotus obliquus on M1 to M2 macrophage polarization and its possible 
      underlying mechanism. Lipopolysaccharide (LPS)-activated M1 macrophages exert 
      pro-inflammatory effects and release inflammatory cytokines including interleukin 
      (IL)-1beta and tumor necrosis factor (TNF)-alpha. The model and various groups were 
      treated with different IB concentrations (2.5, 5, and 10 mug/mL) to observe 
      changes in the M1 and M2 phenotypes, gene expression of NAD-dependent deacetylase 
      sirtuin-1 (Sirt1), and endoplasmic reticulum stress (ERS). SIRT1-siRNA and 
      thapsigargin (TG), an ERS agonist, were used to examine the relationship between 
      SIRT1/ERS and the effect of IB on M1 to M2 RAW264.7 macrophage phenotypic 
      changes. We found that IB had no effect on RAW264.7 cell proliferation at 
      10 mug/mL. Increasing concentrations of IB (2.5, 5, and 10 mug/mL) decreased the 
      number of phenotypic M1 macrophages and, consequently, decreased the release of 
      the inflammatory cytokines, IL-1beta and TNF-alpha. Furthermore, IB treatment increased 
      the level of phenotypic M2 macrophages, which increased the release of 
      anti-inflammatory cytokines such as arginase (Arg)-1 and found in inflammatory 
      zone 1 (FIZZ1) in a dose-dependent manner. Further, we found that IB increased 
      the expression of SIRT1 and inhibited that of ERS. Inhibition of Sirt1 expression 
      by siRNA significantly increased that of ERS marker genes and IL1beta. Excessive ERS 
      levels inhibited the IB-induced transformation of phenotypic M1 macrophage to the 
      M2 macrophage phenotype. Therefore, IB, an extract of I. obliquus, may regulate 
      macrophage polarization through the SIRT1/ERS signaling pathway.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Du, Na
AU  - Du N
AD  - Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of 
      Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, 
      China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of 
      Education, Hefei 230032, China.
FAU - Wu, Kun
AU  - Wu K
AD  - Department of Natural Medicine and Chemistry, School of Pharmacy, Anhui Medical 
      University, Hefei 230032, China.
FAU - Zhang, Jin
AU  - Zhang J
AD  - Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of 
      Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, 
      China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of 
      Education, Hefei 230032, China.
FAU - Wang, Lili
AU  - Wang L
AD  - Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of 
      Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, 
      China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of 
      Education, Hefei 230032, China.
FAU - Pan, Xuesheng
AU  - Pan X
AD  - Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of 
      Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, 
      China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of 
      Education, Hefei 230032, China.
FAU - Zhu, Yueqin
AU  - Zhu Y
AD  - Department of Pharmacy, West Branch of The First Affiliated Hospital of 
      University of Science and Technology of China (Anhui Provincial Cancer Hospital), 
      Hefei 230031, China.
FAU - Wu, Xian
AU  - Wu X
AD  - Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of 
      Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, 
      China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of 
      Education, Hefei 230032, China.
FAU - Liu, Jinghao
AU  - Liu J
AD  - Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of 
      Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, 
      China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of 
      Education, Hefei 230032, China.
FAU - Chen, Yun
AU  - Chen Y
AD  - Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of 
      Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, 
      China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of 
      Education, Hefei 230032, China.
FAU - Ye, Ying
AU  - Ye Y
AD  - Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of 
      Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, 
      China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of 
      Education, Hefei 230032, China.
FAU - Wang, Yuanyuan
AU  - Wang Y
AD  - Department of Pharmacology, The Second Hospital of Anhui Medical University, 678 
      Furong Road, Hefei 230601, China.
FAU - Wu, Wenyong
AU  - Wu W
AD  - Department of General Surgery, The First Affiliated Hospital of Anhui Medical 
      University, China.
FAU - Cheng, Wenming
AU  - Cheng W
AD  - Department of Natural Medicine and Chemistry, School of Pharmacy, Anhui Medical 
      University, Hefei 230032, China. Electronic address: 914341547@qq.com.
FAU - Huang, Yan
AU  - Huang Y
AD  - Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of 
      Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, 
      China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of 
      Education, Hefei 230032, China. Electronic address: aydhy@126.com.
LA  - eng
PT  - Journal Article
DEP - 20210405
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Cytokines)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Hspa5 protein, mouse)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (inonotsuoxide B)
RN  - 1J05Z83K3M (Lanosterol)
RN  - EC 2.7.11.1 (Ern1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.1.- (Endoribonucleases)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Cytokines/genetics/metabolism
MH  - Endoplasmic Reticulum Chaperone BiP/genetics/metabolism
MH  - Endoplasmic Reticulum Stress/*drug effects/genetics
MH  - Endoribonucleases/genetics/metabolism
MH  - Lanosterol/*analogs & derivatives/pharmacology
MH  - Lipopolysaccharides/toxicity
MH  - Macrophage Activation/*drug effects
MH  - Macrophages/drug effects/*immunology
MH  - Mice
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - RAW 264.7 Cells
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/genetics/*metabolism
OTO - NOTNLM
OT  - Endoplasmic reticulum stress (ERS)
OT  - Inonotsuoxide B
OT  - M1 and M2 Macrophages
OT  - SIRT1
EDAT- 2021/04/09 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/04/08 20:31
PHST- 2020/12/10 00:00 [received]
PHST- 2021/03/10 00:00 [revised]
PHST- 2021/03/19 00:00 [accepted]
PHST- 2021/04/09 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/04/08 20:31 [entrez]
AID - S1567-5769(21)00239-3 [pii]
AID - 10.1016/j.intimp.2021.107603 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2021 Jul;96:107603. doi: 10.1016/j.intimp.2021.107603. Epub 
      2021 Apr 5.