PI3K/Akt-Beclin1 signaling pathway positively regulates phagocytosis and negatively mediates NF-κB-dependent inflammation in Staphylococcus aureus-infected macrophages.

Abstract

Although autophagy and phagocytosis are involved in the regulation of host inflammatory response to bacterial infection in macrophages, the underlying mechanisms have not been completely elucidated. In the present study, we found that infecting RAW264.7 macrophages with Staphylococcus aureus (S. aureus) activated multiple signaling pathways including phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt), nuclear factor-κB (NF-κB), and Rac1, as well as triggered autophagy. LY294002, a specific PI3K activity inhibitor, significantly decreased autophagy and phagocytosis of macrophages upon S. aureus infection. Similarly, knockdown of Beclin1 by specific siRNA significantly inhibited autophagy and phagocytosis of S. aureus-infected macrophages. Additionally, we showed that although administration of Beclin1 siRNA had no effects on phosphorylation of Akt (p-Akt), inhibition of PI3K activity by LY294002 significantly decreased the expression of Beclin1, suggesting that Beclin1 is a downstream molecular of PI3K. Furthermore, inhibition of autophagy significantly increased the production of NF-κB-dependent TNFα/IL-1β in S. aureus-infected macrophages. Collectively, these findings demonstrated, for the first time, that the PI3K/Akt-Beclin1 signaling pathway positively regulates phagocytosis and negatively mediates NF-κB-dependent inflammation in S. aureus-infected macrophages.

• Authors: Yunxiang Lv, Lei Fang, Peishan Ding, Rongyu Liu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 510 Issue 2 Pg. 284-289 (03 05 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 30700382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Beclin-1
• Becn1 protein, mouse
• IL1B protein, mouse
• Interleukin-1beta
• NF-kappa B p50 Subunit
• Tumor Necrosis Factor-alpha
• Nfkb1 protein, mouse
• Phosphatidylinositol 3-Kinases
• Adenylate Kinase
• adenylate kinase 1

Topics

• Adenylate Kinase (metabolism)
• Animals
• Autophagy
• Beclin-1 (metabolism)
• Interleukin-1beta (metabolism)
• Macrophages (metabolism, microbiology)
• Mice
• NF-kappa B p50 Subunit (metabolism)
• Phagocytosis
• Phosphatidylinositol 3-Kinases (metabolism)
• RAW 264.7 Cells
• Signal Transduction
• Staphylococcal Infections (metabolism)
• Staphylococcus aureus
• Tumor Necrosis Factor-alpha (metabolism)