Recombinant human brain natriuretic peptide attenuates LPS-induced cellular injury in human fetal lung fibroblasts via inhibiting MAPK and NF-κB pathway activation

Zhi Song, Xiu Zhao, Martin Liu, Hongxu Jin, Yan Cui, Mingxiao Hou, Yan Gao

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Inflammatory responses are vital in lung injury diseases, particularly acute respiratory distress syndrome (ARDS). Recombinant human brain natriuretic peptide (rhBNP) has been shown to exhibit anti-inflammatory effects in vivo in our previous studies. The present study aimed to investigate the mechanisms underlying the anti-inflammatory effects of rhBNP on lipopolysaccharide (LPS)-induced human fetal lung fibroblasts (HFL-1). The results showed that LPS induced a significant increase in the leakage of lactate dehydrogenase and the secretion of interleukin (IL)-1β. Activation of p38, extracellular-signal regulated kinase (ERK) 1/2, c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinases (MAPK)s, and nuclear factor (NF)-κB in HFL-1 cells was also observed following treatment with LPS. Treatment with rhBNP (0.1 μM) reduced the production of IL-1β at the protein and mRNA levels. Moreover, rhBNP decreased the phosphorylation of p38, ERK1/2 and JNK induced by LPS. However, the JNK inhibitor, SP600125, significantly inhibited LPS-induced IL-1β production. These results indicate that the inhibition of IL-1β by may dependent upon the JNK signaling pathway. The LPS-induced NF-κB activation was also suppressed by rhBNP, and IL-1β production was inhibited by the NF-κB inhibitor. Furthermore, NF-κB activation was attenuated by the JNK inhibitor, indicating that NF-κB activation was dependent on the JNK signaling pathway. The present study suggests that rhBNP exhibits an anti-inflammatory effect on LPS-induced HFL-1 cell injury via the inhibition of MAPK and NF-κB signaling pathways and may exhibit therapeutic potential for acute lung injury and ARDS.

Original languageEnglish (US)
Pages (from-to)1785-1790
Number of pages6
JournalMolecular Medicine Reports
Volume14
Issue number2
DOIs
StatePublished - Aug 2016

Keywords

  • Human fetal lung fibroblasts
  • Lipopolysaccharide
  • Mitogen-activated protein kinase
  • Nuclear factor-κB
  • Recombinant human brain natriuretic peptide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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