PMID- 31582904
OWN - NLM
STAT- MEDLINE
DCOM- 20200323
LR  - 20200323
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2019
DP  - 2019
TI  - Pregnancy-Associated Plasma Protein A Induces Inflammatory Cytokine Expression by 
      Activating IGF-I/PI3K/Akt Pathways.
PG  - 8436985
LID - 10.1155/2019/8436985 [doi]
LID - 8436985
AB  - Pregnancy-associated plasma protein A (PAPP-A) was previously reported to be an 
      inflammatory biomarker and a prognostic marker of acute coronary syndrome (ACS) 
      and involved in the process of atherosclerosis and plaque rupture. However, the 
      role of PAPP-A in inflammation is poorly understood. In this study, we aimed to 
      investigate the role of PAPP-A in macrophage activation and inflammatory cytokine 
      production. RAW264.7 macrophages were treated with or without PAPP-A. 
      Reverse-transcriptase quantitative real-time PCR (RT-qPCR) and Western blot were 
      performed to detect gene and protein expressions. The concentration of monocyte 
      chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), and 
      interleukin-6 (IL-6) in culture supernatants was determined by ELISA. Results 
      showed that PAPP-A significantly stimulated the expression of MCP-1, TNF-alpha, and 
      IL-6 at both transcriptional and translational levels in a dose-dependent and 
      time-dependent manner. The secretion of these inflammatory cytokines by 
      macrophages was also increased after PAPP-A treatment. Moreover, PAPP-A activated 
      the IGF-I/PI3K/Akt signaling pathway in macrophages. The PAPP-A-mediated 
      upregulation of MCP-1, TNF-alpha, and IL-6 mRNA and protein levels were strongly 
      inhibited by PI3K inhibitors or IGF-IR siRNA, indicating that the upregulation of 
      MCP-1, TNF-alpha, and IL-6 could involve the IGF-I/PI3K/Akt pathway. Together, this 
      study demonstrates that PAPP-A activates the macrophage signaling pathway 
      (IGF-I/PI3K/Akt), which drives the expression and production of inflammatory 
      cytokines known to contribute to the initiation and progression of ACS. These 
      findings indicate that PAPP-A may play a proinflammatory role in the 
      pathophysiology of ACS and serve as a potential therapeutic target.
CI  - Copyright (c) 2019 Weiping Li et al.
FAU - Li, Weiping
AU  - Li W
AUID- ORCID: 0000-0002-5534-5925
AD  - Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, 
      Capital Medical University, Beijing 100050, China.
AD  - Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease, 
      Beijing 100069, China.
FAU - Li, Hongwei
AU  - Li H
AD  - Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, 
      Capital Medical University, Beijing 100050, China.
AD  - Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease, 
      Beijing 100069, China.
AD  - Department of Internal Medicine, Medical Health Center, Beijing Friendship 
      Hospital, Capital Medical University, Beijing 100050, China.
FAU - Zhou, Li
AU  - Zhou L
AD  - Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, 
      Capital Medical University, Beijing 100050, China.
FAU - Wang, Zijian
AU  - Wang Z
AD  - Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, 
      Capital Medical University, Beijing 100050, China.
FAU - Hua, Bing
AU  - Hua B
AD  - Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, 
      Capital Medical University, Beijing 100050, China.
LA  - eng
PT  - Journal Article
DEP - 20190910
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.24.- (Pregnancy-Associated Plasma Protein-A)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - Cytokines/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Interleukin-6/metabolism
MH  - Mice
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Pregnancy-Associated Plasma Protein-A/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - RAW 264.7 Cells
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC6754940
COIS- The authors declared they do not have anything to disclose regarding the conflict 
      of interest with respect to this manuscript.
EDAT- 2019/10/05 06:00
MHDA- 2020/03/24 06:00
PMCR- 2019/09/10
CRDT- 2019/10/05 06:00
PHST- 2019/04/09 00:00 [received]
PHST- 2019/07/10 00:00 [revised]
PHST- 2019/08/13 00:00 [accepted]
PHST- 2019/10/05 06:00 [entrez]
PHST- 2019/10/05 06:00 [pubmed]
PHST- 2020/03/24 06:00 [medline]
PHST- 2019/09/10 00:00 [pmc-release]
AID - 10.1155/2019/8436985 [doi]
PST - epublish
SO  - Mediators Inflamm. 2019 Sep 10;2019:8436985. doi: 10.1155/2019/8436985. 
      eCollection 2019.