1. Academic Validation
  2. Phosphatidylserine-Specific Phospholipase A1 Alleviates Lipopolysaccharide-Induced Macrophage Inflammation by Inhibiting MAPKs Activation

Phosphatidylserine-Specific Phospholipase A1 Alleviates Lipopolysaccharide-Induced Macrophage Inflammation by Inhibiting MAPKs Activation

  • Biol Pharm Bull. 2022 Aug 1;45(8):1061-1068. doi: 10.1248/bpb.b22-00001.
Wei Zhang 1 2 Chao Liu 2 Mengmeng Wang 2 Zhizhou Yang 1 2 Jian Yang 3 Yi Ren 2 Liping Cao 2 Xiaoqin Han 2 Limin Huang 2 Zhaorui Sun 2 Shinan Nie 1 2
Affiliations

Affiliations

  • 1 Department of Emergency Medicine, Jinling Clinical Medical College of Nanjing Medical University.
  • 2 Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University.
  • 3 Department of Radiology, Zhongda Hospital, Jiangsu Key Laboratory of Molecular and Functional Imaging, Medical School of Southeast University.
Abstract

Macrophages are a key in innate immune responses and play vital roles in homeostasis and inflammatory diseases. Phosphatidylserine-specific Phospholipase A1 (PS-PLA1) is a specific Phospholipase which hydrolyzes fatty acid from the sn-1 position of phosphatidylserine (PS) to produce lysophosphatidylserine (lysoPS). Both PS and lysoPS are associated with activation of immune cells including macrophages. However, the effect of PS-PLA1 on macrophage inflammation remains unclear. The purpose of this study is to evaluate the role of PS-PLA1 in lipopolysaccharide (LPS)-induced macrophage inflammation. Alterations of PS-PLA1 expression in LPS-stimulated RAW264.7 macrophages were investigated via Western blot. PS-PLA1 stable knockdown and overexpression RAW264.7 cell lines were generated by infecting cells with appropriate lentiviral vectors, respectively. PS-PLA1 expression was found to be dramatically upregulated in RAW264.7 macrophages after LPS stimulation. PS-PLA1 knockdown promotes while PS-PLA1 overexpression ameliorates the release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nitric oxide from RAW264.7 cells and M1 macrophage polarization. Additionally, PS-PLA1 knockdown facilitates phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), while PS-PLA1 overexpression attenuates their phosphorylation. Moreover, mitogen-activated protein kinase (MAPK) inhibitors block the release of TNF-α and IL-1β in PS-PLA1 knockdown RAW264.7 cells after LPS stimulation. These findings suggest PS-PLA1 ameliorates LPS-induced macrophage inflammation by inhibiting MAPKs activation, and PS-PLA1 might be considered as a target for modulating macrophage inflammation.

Keywords

inflammation; lipopolysaccharide; macrophage; mitogen-activated protein kinase; phosphatidylserine-specific phospholipase A1.

Figures
Products