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Yan Sun; Regulation of neutrophil processing of IL-1b in fungal keratitis Yan Sun1, Steven De Jesus Carrion1, Chengye Che2, Eric Pearlman11Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA; 2Department of Ophthalmology, Qingdao University, Qingdao, China.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4036.
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IL-1b is transcribed as an inactive 37kD protein, and cleaved by caspase-1 to the 17kD bioactive form, which is secreted from the cells. The purpose of this study was to determine the role of neutrophils and IL-1b in fungal keratitis, and to understand the mechanism of IL-1b processing by neutrophils.
C57BL/6 and IL-1b-/- mice were infected intrastromally with red fluorescent protein (RFP) expressing Aspergillus fumigatus spores, and corneal opacity, fungal growth was examined. Also, bone marrow neutrophils were isolated from C57BL/6 and gene knockout mice, stimulated with A. fumigatus, and the IL-1b 37kD and 17kD forms were detected by western blot.
IL-1b-/- mice had elevated CFU compared with C57BL/6 mice, and neutrophils were the predominant source of IL-1b in infected corneas 24h post-infection. A. fumigatus induced IL-1b processing by bone marrow neutrophils was dependent on Dectin-1 mediated production of IFN-b through the Raf-1/MEK/ERK pathway rather than the canonical spleen tyrosine kinase (Syk) pathway. Activation of the IFN- a/b receptor stimulated caspase-11, which was required for caspase-1 mediated cleavage and secretion of IL-1b.
We identify an essential role for neutrophil derived IL-1b in the protective immune response in fungal keratitis, and characterize the mechanism of IL-1b processing in these cells. These findings reveal potential targets for therapeutic intervention in this disease.<br />
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