PDX regulates inflammatory cell infiltration via resident macrophage in LPS‐induced lung injury

Abstract

Inflammatory cell infiltration contributes to the pathogenesis of acute respiratory distress syndrome (ARDS). Protectin DX (PDX), an endogenous lipid mediator, shows anti‐inflammatory and proresolution bioactions. In vivo, the mice were intraperitoneally injected with PDX (0.1 µg/mouse) after intratracheal (1 mg/kg) or intraperitoneal (10 mg/kg) LPS administration. Flow cytometry was used to measure inflammatory cell numbers. Clodronate liposomes were used to deplete resident macrophages. RT‐PCR, and ELISA was used to measure MIP‐2, MCP‐1, TNF‐α and MMP9 levels. In vitro, sorted neutrophils, resident and recruited macrophages (1 × 106) were cultured with 1 μg/mL LPS and/or 100 nmol/L PDX to assess the chemokine receptor expression. PDX attenuated LPS‐induced lung injury via inhibiting recruited macrophage and neutrophil recruitment through repressing resident macrophage MCP‐1, MIP‐2 expression and release, respectively. Finally, PDX inhibition of neutrophil infiltration and transmembrane was associated with TNF‐α/MIP‐2/MMP9 signalling pathway. These data suggest that PDX attenuates LPS‐stimulated lung injury via reduction of the inflammatory cell recruitment mediated via resident macrophages.

Protectin DX promotes the inflammatory resolution via activating COX-2/L-PGDS-PGD2 and DP1 receptor in acute respiratory distress syndrome

“…PDX exerts its effects via ALX receptor pathways. [25] , [26] , [27] Thus, our study used the ALX antagonist BOC-2. As expected, the ALX antagonist reversed the PDX induced improvement on COX-2/L-PGDS-PGD 2 expression both in vivo and in vitro , suggesting that PDX up-regulates COX-2/L-PGDS-PGD 2 signaling via the ALX/FPR2 receptor.…”

“… [25] PDX regulates inflammatory cell infiltration via resident macrophage in LPS-induced lung injury. [26] Moreover, PDX was shown to alleviate lung injury induced by LPS via inducing primary rat type II alveolar epithelial cells proliferation and inhibiting their apoptosis in vivo and in vitro . [27] …”

Protectin DX Attenuates Lumbar Radicular Pain of Non-compressive Disc Herniation by Autophagy Flux Stimulation via Adenosine Monophosphate-Activated Protein Kinase Signaling

“…Protectin DX is described as a newly identified SPM ( Sanceau et al, 2019 ). Emerging studies revealed that PDX could facilitate the resolution of inflammation by driving macrophage emigration, phagocytosis, and M2 polarization ( Xia et al, 2017 ; Ye et al, 2020 ). Moreover, PDX has been found to control progressive inflammation by suppressing platelet aggregation and preventing leukocyte infiltration and oxidative stress ( Stein et al, 2016 ; Hwang et al, 2019 ).…”

γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury

“…After the onset of inflammation, neutrophils and macrophages produce a series of SPMs, including lipoxins, resolvins, protectins, and maresins (16). These SPMs inhibit the excessive infiltration of neutrophils and help orchestrate the return to homeostasis (34)(35)(36). Transcriptome profiling in this study suggested that MCTR1 decreased neutrophil infiltration in which the IL-17 signaling pathway involved, and we confirmed that MCTR1 reduced the expression levels of G-CSF and CXCL1 which regulated neutrophil chemotaxis, decreased neutrophil recruitment in LPS-injured heart.…”