Lipoxin A4 attenuates hyperoxia‑induced lung epithelial cell injury via the upregulation of heme oxygenase‑1 and inhibition of proinflammatory cytokines.

The present study examined whether lipoxin A4 (LXA4) increases the expression of HO‑1, and inhibits the production of interleukin 6 (IL‑6) and monocyte chemotactic protein 1 (MCP‑1) in LXA4‑induced protection during hyperoxia‑induced injury in murine lung epithelial cells (MLE‑12) and what signal pathway may participate in the actions of LXA4 inhibiting IL‑6 and MCP‑1. MLE‑12 cells were exposed to air or hyperoxia with or without pretreatment with LXA4, Zinc protoporphyrin IX (ZnPP‑IX), IL‑6, anti‑IL‑6, MCP‑1, anti‑MCP‑1, inhibitors of p38 mitogen‑activated protein kinase (p38 MAPK), protein kinase B (Akt) and extracellular signal‑regulated kinase 1/2 (ERK1/2) signaling pathways. The cell survival rates, cell viability, apoptosis rates, expression of superoxide dismutase (SOD), heme oxygenase‑1 (HO‑1), IL‑6 and MCP‑1, and the activations of p38 MAPK, ERK1/2 and Akt were measured. LXA4 significantly increased the cell survival rates, cell viability, SOD levels and HO‑1 expression, reduced the apoptosis rates, and inhibited the MCP‑1 and IL‑6 levels induced by hyperoxia in cells. ZnPP‑IX, an inhibitor of HO‑1, blocked LXA4‑induced protection on cell viability in cells exposed to hyperoxia. Anti‑IL‑6 and anti‑MCP‑1 improved the cell viability of cells exposed to hyperoxia. Inhibition of p38 MAPK and ERK1/2 blocked the expression of MCP‑1 and IL‑6 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 hyperoxia‑induced injury in MLE‑12 cells via the upregulation of HO‑1 expression. The protection of LXA4 in hyperoxia‑induced cell injury may be associated with the downregulation IL‑6 and MCP‑1 levels via the inhibition of the p38 MAPK and ERK1/2 signaling pathways.

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