Lipoxin A4 attenuates hyperoxiainduced lung epithelial cell injury via the upregulation of heme oxygenase1 and inhibition of proinflammatory cytokines.
Mol Med Rep
; 21(1): 429-437, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31746387
ABSTRACT
The present study examined whether lipoxin A4 (LXA4) increases the expression of HO1, and inhibits the production of interleukin 6 (IL6) and monocyte chemotactic protein 1 (MCP1) in LXA4induced protection during hyperoxiainduced injury in murine lung epithelial cells (MLE12) and what signal pathway may participate in the actions of LXA4 inhibiting IL6 and MCP1. MLE12 cells were exposed to air or hyperoxia with or without pretreatment with LXA4, Zinc protoporphyrin IX (ZnPPIX), IL6, antiIL6, MCP1, antiMCP1, inhibitors of p38 mitogenactivated protein kinase (p38 MAPK), protein kinase B (Akt) and extracellular signalregulated kinase 1/2 (ERK1/2) signaling pathways. The cell survival rates, cell viability, apoptosis rates, expression of superoxide dismutase (SOD), heme oxygenase1 (HO1), IL6 and MCP1, and the activations of p38 MAPK, ERK1/2 and Akt were measured. LXA4 significantly increased the cell survival rates, cell viability, SOD levels and HO1 expression, reduced the apoptosis rates, and inhibited the MCP1 and IL6 levels induced by hyperoxia in cells. ZnPPIX, an inhibitor of HO1, blocked LXA4induced protection on cell viability in cells exposed to hyperoxia. AntiIL6 and antiMCP1 improved the cell viability of cells exposed to hyperoxia. Inhibition of p38 MAPK and ERK1/2 blocked the expression of MCP1 and IL6 induced by hyperoxia. LXA4 inhibited the activation of p38 MAPK and ERK1/2 induced by hyperoxia, and increased the activation of the Akt signaling pathway, which was inhibited by hyperoxia. Therefore, LXA4 attenuated hyperoxiainduced injury in MLE12 cells via the upregulation of HO1 expression. The protection of LXA4 in hyperoxiainduced cell injury may be associated with the downregulation IL6 and MCP1 levels via the inhibition of the p38 MAPK and ERK1/2 signaling pathways.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quimiocina CCL2
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Lipoxinas
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Heme Oxigenase-1
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Lesão Pulmonar
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2020
Tipo de documento:
Article