Polydeoxyribonucleotide ameliorates lipopolysaccharide-induced acute lung injury via modulation of the MAPK/NF-κB signaling pathway in rats

Il Gyu Ko, Jae Joon Hwang, Bok Soon Chang, Sang Hoon Kim, Jun Jang Jin, Lakkyong Hwang, Chang Ju Kim, Cheon Woong Choi

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Acute lung injury (ALI) is characterized by disruption of the alveolar-capillary membrane resulting in pulmonary edema and accumulation of associated proteinaceous alveolar exudate. Initiation of ALI upregulates tumor necrosis factor-α (TNF-α), which activates nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) that induce various pro-inflammatory mediators. Polydexyribonucleotide (PDRN) is an adenosine A2A receptor agonist that exerts anti-inflammatory effects by suppressing the production of pro-inflammatory cytokines and apoptosis. We investigated the therapeutic efficiency of PDRN on ALI induced by lipopolysaccharide (LPS) in rats. ALI was induced by intratracheal instillation of LPS (5 mg/kg) in 200 μL saline. The PDRN treatment group received a single intraperitoneal injection of 500 μL saline including PDRN (8 mg/kg) 1 h after ALI induction. To confirm the involvement of the adenosine A2A receptor in PDRN, 8 mg/kg 7-dimethyl-1-propargylxanthine (DMPX) was applied with PDRN treatment. Rats were then sacrificed 12 h after PDRN and DMPX treatments. Intratracheal administration of LPS caused lung tissue damage and significantly increased the lung injury scores and levels of pro-inflammatory cytokines, and apoptotic factors. In addition, MAPK/NF-κB signaling factors were increased by ALI initiation. PDRN treatment potently suppressed expressions of MAPK/NF-κB signaling factors compared to the PDRN + DMPX co-treated group. These alterations led to a reduction of pro-inflammatory cytokines, apoptotic factors, and NF-κB and MAPK signaling, which promoted the recovery of damaged lung tissue. PDRN therapy demonstrated therapeutic effects for LPS-induced ALI compared to the non-treated and DMPX-treated groups. Therefore, PDRN may be used as a therapy for initial treatment of ALI.

Original languageEnglish
Article number106444
JournalInternational Immunopharmacology
Volume83
DOIs
Publication statusPublished - Jun 2020

Keywords

  • Acute lung injury
  • Apoptosis
  • Inflammation
  • Mitogen-activated protein kinases
  • Nuclear factor-kappa B
  • Polydexyribonucleotide

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