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Int Immunopharmacol. 2022 Jan;102:108348. doi: 10.1016/j.intimp.2021.108348. Epub 2021 Nov 10.

Protectin DX promotes the inflammatory resolution via activating COX-2/L-PGDS-PGD.

International immunopharmacology

Xin Hu, Ye-An Zhang, Ben Chen, Zi Jin, Mei-Lin Lin, Ming Li, Hong-Xia Mei, Jia-Chao Lu, Yu-Qiang Gong, Sheng-Wei Jin, Sheng-Xing Zheng

Affiliations

  1. Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China.
  2. Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. Electronic address: [email protected].
  3. Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. Electronic address: [email protected].
  4. Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. Electronic address: [email protected].

PMID: 34920958 PMCID: PMC8578004 DOI: 10.1016/j.intimp.2021.108348

Abstract

PURPOSE: Acute respiratory distress syndrome (ARDS) is characterized by uncontrollable inflammation. Cyclooxygenase-2(COX-2) and its metabolite prostaglandins are known to promote the inflammatory resolution of ARDS. Recently, a newly discovered endogenous lipid mediator, Protectin DX (PDX), was also shown to mediate the resolution of inflammation. However, the regulatory of PDX on the pro-resolving COX-2 in ARDS remains unknown.

MATERIAL AND METHODS: PDX (5 μg/kg) was injected into rats intravenously 12 h after the lipopolysaccharide (LPS, 3 mg/kg) challenge. Primary rat lung fibroblasts were incubated with LPS (1 μg/ml) and/or PDX (100 nM). Lung pathological changes examined using H&E staining. Protein levels of COX-2, PGDS and PGES were evaluated using western blot. Inflammatory cytokines were tested by qPCR, and the concentration of prostaglandins measured by using ELISA.

RESULTS: Our study revealed that, COX-2 and L-PGDS has biphasic activation characteristics that LPS could induce induced by LPS both in vivo and in vitro.. The secondary peak of COX-2, L-PGDS-PGD

CONCLUSION: PDX promoted the resolution of inflammation of ARDS model via enhancing the expression of secondary peak of COX-2/L-PGDS-PGD

Copyright © 2021. Published by Elsevier B.V.

Keywords: Acute respiratory distress syndrome; Cyclooxygenase-2; Inflammatory resolution; Lipocalin-type prostaglandin D synthase; Protectin DX

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