Recombinant adiponectin protects the newborn rat lung from lipopolysaccharide-induced inflammatory injury

Julijana Ivanovska, Na Young Cindy Kang, Nikola Ivanovski, Avita Nagy, Jaques Belik, Estelle B. Gauda

Research output: Contribution to journalArticlepeer-review

Abstract

Preterm infants are at high risk for developing bronchopulmonary dysplasia and pulmonary hypertension from inflammatory lung injury. In adult models, adiponectin (APN)—an adipocyte-derived hormone—protects the lung from inflammatory injury and pulmonary vascular remodeling. Cord blood APN levels in premature infants born < 26 weeks gestation are 5% of the level in infants born at term. We previously reported the expression profile of APN and its receptors in neonatal rat lung homogenates during the first 3 weeks of postnatal development. Here, we characterize the expression profile of APN and its receptors in specific lung cells and the effects of exogenous recombinant APN (rAPN) on lipopolysaccharide-(LPS)-induced cytokine and chemokine production in total lung homogenates and specific lung cells. In vitro, rAPN added to primary cultures of pulmonary artery smooth muscle cells attenuated the expression of LPS-induced pro-inflammatory cytokines while increasing the expression of anti-inflammatory cytokines. In vivo, intraperitoneal rAPN (2 mg/kg), given 4 hr prior to intrapharyngeal administration of LPS (5 mg/kg) to newborn rats at postnatal day 4, significantly reduced gene and protein expression of the pro-inflammatory cytokine IL-1ß and reduced protein expression of the chemokines monocyte chemoattractant protein (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1α) in the lung. LPS-induced histopathological changes in the lung were also decreased. Moreover, rAPN given 20 hr after intrapharyngeal LPS had a similar effect on lung inflammation. These findings suggest a role for APN in protecting the lung from inflammation during early stages of lung development.

Original languageEnglish (US)
Article numbere14553
JournalPhysiological Reports
Volume8
Issue number17
DOIs
StatePublished - Sep 1 2020

Keywords

  • adiponectin
  • adiponectin receptors 1 and 2
  • bronchopulmonary dysplasia
  • chemokines
  • cytokines
  • neonatal rat

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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