Min Cheng1, Jing Lin2, Cui Li2, Wenyi Zhao2, Hua Yang2, Leyu Lv2, Chengye Che3. 1. Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China; Department of Ophthalmology, Laixi Municipal Hospital, Qingdao, Shandong Province, China. 2. Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. 3. Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. Electronic address: chechengye@126.com.
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.
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. fumigatusinfection. 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. fumigatuskeratitis. 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.