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

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.

journal_name

Mol Med Rep

journal_title

Molecular medicine reports

authors

Song Z,Zhao X,Liu M,Jin H,Cui Y,Hou M,Gao Y

doi

10.3892/mmr.2016.5400

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

1785-90

issue

eissn

1791-2997

issn

1791-3004

journal_volume

pub_type

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