PMID- 36613764
OWN - NLM
STAT- MEDLINE
DCOM- 20230110
LR  - 20230111
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 1
DP  - 2022 Dec 24
TI  - Salicylate Sodium Suppresses Monocyte Chemoattractant Protein-1 Production by 
      Directly Inhibiting Phosphodiesterase 3B in TNF-alpha-Stimulated Adipocytes.
LID - 10.3390/ijms24010320 [doi]
LID - 320
AB  - As a worldwide health issue, obesity is associated with the infiltration of 
      monocytes/macrophages into the adipose tissue causing unresolved inflammation. 
      Monocyte chemoattractant protein-1 (MCP-1) exerts a crucial effect on 
      obesity-related monocytes/macrophages infiltration. Clinically, aspirin and 
      salsalate are beneficial for the treatment of metabolic diseases in which adipose 
      tissue inflammation plays an essential role. Herein, we investigated the effect 
      and precise mechanism of their active metabolite salicylate on TNF-alpha-elevated 
      MCP-1 in adipocytes. The results indicated that salicylate sodium (SAS) could 
      lower the level of MCP-1 in TNF-alpha-stimulated adipocytes, which resulted from a 
      previously unrecognized target phosphodiesterase (PDE), 3B (PDE3B), rather than 
      its known targets IKKbeta and AMPK. The SAS directly bound to the PDE3B to 
      inactivate it, thus elevating the intracellular cAMP level and activating PKA. 
      Subsequently, the expression of MKP-1 was increased, which led to the decrease in 
      p-EKR and p-p38. Both PDE3B silencing and the pharmacological inhibition of 
      cAMP/PKA compromised the suppressive effect of SAS on MCP-1. In addition to 
      PDE3B, the PDE3A and PDE4B activity was also inhibited by SAS. Our findings 
      identify a previously unrecognized pathway through which SAS is capable of 
      attenuating the inflammation of adipocytes.
FAU - Zhang, Xiaoyu
AU  - Zhang X
AD  - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Beijing 100193, China.
FAU - Gao, Yuan
AU  - Gao Y
AD  - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Beijing 100193, China.
FAU - Liu, Zhuangzhuang
AU  - Liu Z
AD  - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Beijing 100193, China.
FAU - Li, Wenjing
AU  - Li W
AD  - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Beijing 100193, China.
FAU - Kang, Yuan
AU  - Kang Y
AD  - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Beijing 100193, China.
FAU - Li, Ximeng
AU  - Li X
AD  - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Beijing 100193, China.
FAU - Xu, Zhenlu
AU  - Xu Z
AD  - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Beijing 100193, China.
FAU - Peng, Cheng
AU  - Peng C
AD  - School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 
      610075, China.
FAU - Qi, Yun
AU  - Qi Y
AUID- ORCID: 0000-0001-7860-6932
AD  - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Beijing 100193, China.
LA  - eng
GR  - 2021-I2M-1-028/CAMS Innovation Fund for Medical Sciences (CIFMS)/
GR  - M21014/Beijing Natural Science Foundation/
GR  - 82074091/National Natural Science Foundation of China/
GR  - 2022ZYXK2011017/Open Research Fund of Chengdu University of Traditional Chinese 
      Medicine State Key Laboratory Southwestern Chinese Medicine Resources/
PT  - Journal Article
DEP - 20221224
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 3)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Salicylates)
SB  - IM
MH  - Humans
MH  - Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism
MH  - *Chemokine CCL2/metabolism
MH  - *Tumor Necrosis Factor-alpha/metabolism
MH  - Adipocytes/metabolism
MH  - Inflammation/metabolism
MH  - Obesity/metabolism
MH  - Salicylates/pharmacology
PMC - PMC9820166
OTO - NOTNLM
OT  - MKP-1
OT  - cAMP
OT  - metaflammation
OT  - p-ERK
OT  - p-p38
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/09 06:00
MHDA- 2023/01/11 06:00
PMCR- 2022/12/24
CRDT- 2023/01/08 01:21
PHST- 2022/11/22 00:00 [received]
PHST- 2022/12/20 00:00 [revised]
PHST- 2022/12/21 00:00 [accepted]
PHST- 2023/01/08 01:21 [entrez]
PHST- 2023/01/09 06:00 [pubmed]
PHST- 2023/01/11 06:00 [medline]
PHST- 2022/12/24 00:00 [pmc-release]
AID - ijms24010320 [pii]
AID - ijms-24-00320 [pii]
AID - 10.3390/ijms24010320 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Dec 24;24(1):320. doi: 10.3390/ijms24010320.