Pregnancy-Associated Plasma Protein A Induces Inflammatory Cytokine Expression by Activating IGF-IPI3KAkt Pathways
Joint Authors
Li, Weiping
Li, Hongwei
Zhou, Li
Wang, Zijian
Hua, Bing
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-09-10
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
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-α (TNF-α), 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-α, 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-α, 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-α, 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.
American Psychological Association (APA)
Li, Weiping& Li, Hongwei& Zhou, Li& Wang, Zijian& Hua, Bing. 2019. Pregnancy-Associated Plasma Protein A Induces Inflammatory Cytokine Expression by Activating IGF-IPI3KAkt Pathways. Mediators of Inflammation،Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1193478
Modern Language Association (MLA)
Li, Weiping…[et al.]. Pregnancy-Associated Plasma Protein A Induces Inflammatory Cytokine Expression by Activating IGF-IPI3KAkt Pathways. Mediators of Inflammation No. 2019 (2019), pp.1-12.
https://search.emarefa.net/detail/BIM-1193478
American Medical Association (AMA)
Li, Weiping& Li, Hongwei& Zhou, Li& Wang, Zijian& Hua, Bing. Pregnancy-Associated Plasma Protein A Induces Inflammatory Cytokine Expression by Activating IGF-IPI3KAkt Pathways. Mediators of Inflammation. 2019. Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1193478
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1193478