Recombinant human brain natriuretic peptide attenuates LPS-induced cellular injury in human fetal lung fibroblasts via inhibiting MAPK and NF-κB pathway activation.
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.
Department of Emergency and Critical Care Medicine, The General Hospital of Shenyang Military, Shenyang, Liaoning 110016, P.R. China.
Zhi
Z
Song
Department of Oral Medicine, The Shenyang Medical College, Shenyang, Liaoning 110034, P.R. China.
Xiu
X
Zhao
Division of Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Martin
M
Liu
Department of Emergency and Critical Care Medicine, The General Hospital of Shenyang Military, Shenyang, Liaoning 110016, P.R. China.
Hongxu
H
Jin
Department of Emergency and Critical Care Medicine, The General Hospital of Shenyang Military, Shenyang, Liaoning 110016, P.R. China.
Yan
Y
Cui
Department of Emergency and Critical Care Medicine, The General Hospital of Shenyang Military, Shenyang, Liaoning 110016, P.R. China.
Mingxiao
M
Hou
Department of Emergency and Critical Care Medicine, The General Hospital of Shenyang Military, Shenyang, Liaoning 110016, P.R. China.
Yan
Y
Gao
D002460:Cell Line; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D020097:Natriuretic Peptide, Brain; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases