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

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-PGD₂ promoted the inflammatory resolution in ARDS model with the DP₁ receptor being activated and PDX up-regulated the inflammatory resolutionvia enhancing the secondary peak of COX-2/L-PGDS-PGD₂ and activating the DP₁ receptor.

Conclusion

PDX promoted the resolution of inflammation of ARDS model via enhancing the expression of secondary peak of COX-2/L-PGDS-PGD₂ and activating the DP₁ receptor. PDX shows promising therapeutic potential in the clinical management of ARDS.

SUBMITTER: Hu X

PROVIDER: S-EPMC8578004 | biostudies-literature |

REPOSITORIES: biostudies-literature

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