Interleukin-37 Attenuates Lipopolysaccharide (LPS)-Induced Neonatal Acute Respiratory Distress Syndrome in Young Mice via Inhibition of Inflammation and Cell Apoptosis.

Abstract

BACKGROUND Neonatal acute respiratory distress syndrome (ARDS) is a common clinical syndrome caused by lung immaturity and the abnormal synthesis of pulmonary surfactant in preterm newborns, and it has high morbidity and mortality rates. The present study investigated the roles of interleukin-37 (IL-37) in the pathogenesis of neonatal ARDS and the underlying biochemical mechanism. MATERIAL AND METHODS We used 6-day-old neonatal C57BL/6 mice to establish the ARDS model. Inflammatory cytokines levels were measured with enzyme-linked immunosorbent assay (ELISA) Kits. The pathological morphology of lung tissues was observed by hematoxylin-eosin (HE) staining. The expression levels of proteins were assessed by Western blotting and apoptotic cells were detected via TUNEL assay. Further, the expression of nucleotide-bound oligomerization domain (Nod)-like receptor P3 (NLRP3) was detected with immunohistochemistry and Western blotting. RESULTS IL-37 attenuated lipopolysaccharide (LPS)-induced cell apoptosis and excessive inflammatory cytokines levels, including IL-1ß, IL-8, TNF-alpha, and MCP-1, and ameliorated lung pathological manifestations in an LPS-induced neonatal ARDS model. Moreover, IL-37 suppressed the abnormal expression of proteins related to the CXCR4/SDF-1 chemokine axis and NLRP3 inflammasome pathway. CONCLUSIONS The present results suggest that IL-37 protect against LPS-induced lung injury through inhibition of inflammation and apoptosis in lung tissue in an LPS-induced neonatal ARDS model. Hence, IL-37 may be considered as a potential therapeutic agent for neonatal ARDS.

• Authors: Bo Li, Xianqiu Ji, Fang Tian, Jingjing Gong, Jie Zhang, Ting Liu
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 26 Pg. e920365 (Mar 10 2020) ISSN: 1643-3750 [Electronic] United States
• PMID: 32152260 (Publication Type: Journal Article)

Chemical References

• Cytokines
• IL37 protein, human
• Inflammasomes
• Interleukin-1
• Lipopolysaccharides
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Recombinant Proteins

Topics

• Animals
• Animals, Newborn
• Apoptosis (drug effects, immunology)
• Bronchoalveolar Lavage Fluid
• Cytokines (metabolism)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Humans
• Inflammasomes (antagonists & inhibitors, metabolism)
• Inflammation (drug therapy, immunology)
• Interleukin-1 (pharmacology, therapeutic use)
• Lipopolysaccharides (immunology)
• Mice
• NLR Family, Pyrin Domain-Containing 3 Protein (antagonists & inhibitors, metabolism)
• Recombinant Proteins (pharmacology, therapeutic use)
• Respiratory Distress Syndrome, Newborn (drug therapy, immunology)
• Signal Transduction (drug effects, immunology)