International immunopharmacology · 2017
Dectin-1 is essential for IL-1β production through JNK activation and apoptosis in Aspergillus fumigatus keratitis.
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Yuan Kelan, Zhao Guiqiu, Che Chengye, Li Cui, Lin Jing, Zhu Guoqiang, He Kun
Аннотация
PURPOSE: To investigate the role of phosphorylated JNK in Dectin-1-induced IL-1β production and the role of Dectin-1 in apoptosis in mouse Aspergillus fumigatus (A. fumigatus) keratitis.
METHODS: Mice corneas were pretreated with Dectin-1 siRNA or SP600125 (the inhibitor of JNK) before A. fumigatus infection. THP-1 macrophages were preincubated with SP600125 before the stimulation of A. fumigatus conidia. Dectin-1, IL-1β, JNK, Bax, Bcl-2, cytochrome-c (cyt-c), caspase-9, caspase-8 and caspase-3 expressions were tested by PCR, Western blot, or Immunofluorescence staining.
RESULTS: Pretreatment with Dectin-1 siRNA significantly decreased A. fumigatus-induced IL-1β production and JNK phosphorylation compared with scrambled control in C57BL/6 mice corneas. SP600125 treatment before infection significantly inhibited IL-1β production compared with DMSO control both in mice corneas and THP-1 macrophages. Furthermore, Dectin-1 deficiency resulted in increased ratio of Bax/Bcl-2, release of cyt-c, activation of caspase-9 and caspase-3 in mouse A. fumigatus keratitis. However, Dectin-1 deficiency didn't affect the activation of caspase-8.
CONCLUSIONS: Being an important inflammatory PRR to mediate host inflammatory response, Dectin-1 induced IL-1β production is JNK dependent in mouse A. fumigatus keratitis, and suppressed apoptosis mediated anti-inflammatory response.
METHODS: Mice corneas were pretreated with Dectin-1 siRNA or SP600125 (the inhibitor of JNK) before A. fumigatus infection. THP-1 macrophages were preincubated with SP600125 before the stimulation of A. fumigatus conidia. Dectin-1, IL-1β, JNK, Bax, Bcl-2, cytochrome-c (cyt-c), caspase-9, caspase-8 and caspase-3 expressions were tested by PCR, Western blot, or Immunofluorescence staining.
RESULTS: Pretreatment with Dectin-1 siRNA significantly decreased A. fumigatus-induced IL-1β production and JNK phosphorylation compared with scrambled control in C57BL/6 mice corneas. SP600125 treatment before infection significantly inhibited IL-1β production compared with DMSO control both in mice corneas and THP-1 macrophages. Furthermore, Dectin-1 deficiency resulted in increased ratio of Bax/Bcl-2, release of cyt-c, activation of caspase-9 and caspase-3 in mouse A. fumigatus keratitis. However, Dectin-1 deficiency didn't affect the activation of caspase-8.
CONCLUSIONS: Being an important inflammatory PRR to mediate host inflammatory response, Dectin-1 induced IL-1β production is JNK dependent in mouse A. fumigatus keratitis, and suppressed apoptosis mediated anti-inflammatory response.