Wedelolactone suppresses IL-1β maturation and neutrophil infiltration in Aspergillus fumigatus keratitis

Abstract

Purpose: Wedelolactone, a chemical compound extracted from Wedelia calendulacea or Eclipta alba, has been reported to regulate key steps in inflammation. However, the effects of wedelolactone on fungal keratitis are not known. Hence, we aimed to characterize the impact of wedelolactone in Aspergillus fumigatus keratitis.

Methods: Aspergillus fumigatus was used to establish an in vivo mouse model of fungal keratitis and an in vitro model of THP-1 macrophages. Mice and THP-1 macrophages were pre-treated with wedelolactone. Clinical evaluation, myeloperoxidase (MPO) assay, neutrophil staining, western blot and quantitative polymerase chain reaction (qRT-PCR) were used to assess the effect of wedelolactone on A. fumigatus infection. Therapeutic effect of natamycin treatment with or without wedelolactone was measured via slit lamp microscopy.

Results: We confirmed that wedelolactone attenuated the infiltration of neutrophils and decreased MPO level at earlier time points in mice with A. fumigatus keratitis. Pre-treatment with wedelolactone decreased pro-inflammatory cytokine interleukin 1 beta (IL-1β) maturation by inhibiting caspase-1 activity. Combined with natamycin, wedelolactone protected corneal transparency in mouse with fungal keratitis.

Conclusion: Present findings indicated that wedelolactone reduced host immune responses by attenuating neutrophil recruitment and IL-1β maturation in Aspergillus fumigatus keratitis. Wedelolactone combined with an antifungal medicine could be a potential therapy for reducing lesion severity in fungal keratitis.

Keywords: Aspergillus fumigatus; Fungal keratitis; IL-1β; Neutrophils; Wedelolactone.