Lipoxin A4 alleviates inflammation in Aspergillus fumigatus–stimulated human corneal epithelial cells by Nrf2/HO-1 signaling pathway

Purpose To investigate the therapeutic effect of lipoxin A4 (LXA4) on Aspergillus fumigatus (A. fumigatus)–stimulated human corneal epithelial cells (HCECs). Methods The cell counting kit-8 (CCK-8) was performed in HCECs to evaluate the toxicity of LXA4. A cell scratch test was used to assess the impact of LXA4 on the migration of HCECs. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were applied to examine the expression of inflammatory mediators in A. fumigatus–stimulated HCECs. The nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and expression in HCECs were detected by immunofluorescence staining. Results LXA4 at 0–10 nmol·L-1 (nM) had no significant cytotoxic effect on HCECs. LXA4 at a concentration of 1 nM and 10 nM significantly promoted the migration rate of HCECs. The mRNA and protein levels of pro-inflammatory mediators, including IL-1β, TNF-α, and IL-6, were remarkably lower in the LXA4-treated group. LXA4 promoted the expression of Nrf2 and heme oxygenase 1 (HO-1) in A. fumigatus–stimulated HCECs compared with the PBS control group. Pretreatment with brusatol (BT, Nrf2 inhibitor) or Zine Protoporphyrin (Znpp, HO-1 inhibitor) receded the anti-inflammatory ability of LXA4. Conclusions LXA4 plays a protective role in A. fumigatus–stimulated HCECs by inhibiting the expression of pro-inflammatory mediators through the Nrf2/HO-1 signaling pathway.

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