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Published on: November 20, 2015
Recombinant adiponectin protects the newborn rat lung from lipopolysaccharide-induced inflammatory injury
Julijana Ivanovska1, Na-Young Cindy Kang1, Nikola Ivanovski1
1The Hospital for Sick Children, Division of Neonatology, Department of Pediatrics and Translational Medicine Program, University of Toronto, Toronto, ON, Canada.
Insights
Adiponectin (APN) protects preterm infant lungs from inflammatory injury. Administering recombinant APN reduced inflammatory markers and lung damage in newborn rats, suggesting a therapeutic role for APN in neonatal lung disease.
Area of Science:
- Neonatal physiology
- Pulmonary medicine
- Endocrinology
Background:
- Preterm infants face high risks of bronchopulmonary dysplasia and pulmonary hypertension due to inflammatory lung injury.
- Adiponectin (APN), an adipocyte-derived hormone, demonstrates protective effects against lung inflammation and vascular remodeling in adult models.
- Cord blood APN levels are significantly lower in premature infants born before 26 weeks gestation compared to term infants.
Purpose of the Study:
- To characterize the expression profile of APN and its receptors in specific neonatal rat lung cells.
- To investigate the effects of exogenous recombinant APN (rAPN) on lipopolysaccharide (LPS)-induced inflammation in neonatal rat lungs.
Main Methods:
- In vitro studies using primary cultures of pulmonary artery smooth muscle cells exposed to rAPN and LPS.
- In vivo studies involving intraperitoneal administration of rAPN to newborn rats followed by intrapharyngeal LPS challenge.
- Analysis of gene and protein expression of inflammatory cytokines and chemokines (e.g., IL-1ß, MCP-1, MIP-1α) and assessment of lung histopathology.
Main Results:
- In vitro, rAPN attenuated pro-inflammatory cytokine expression and increased anti-inflammatory cytokine expression in response to LPS.
- In vivo, rAPN administration significantly reduced the expression of IL-1ß, MCP-1, and MIP-1α in the lungs of LPS-exposed newborn rats.
- rAPN treatment decreased LPS-induced lung histopathological damage, regardless of whether it was administered before or after LPS exposure.
Conclusions:
- Adiponectin plays a role in protecting the neonatal lung from inflammation.
- Exogenous recombinant APN demonstrates potential as a therapeutic agent to mitigate inflammatory lung injury in early development.
- These findings support further investigation into APN-based therapies for neonatal lung diseases.
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.
