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Abstract：
BACKGROUND: Clonorchiasis caused by Clonorchis sinensis is a zoonotic parasitic disease characterized by cholangitis, biliary proliferation, biliary fibrosis, and even cholangiocarcinoma. Our previous study showed that the expression of interleukin (IL)-33 is increased in both humans and mice infected by C. sinensis, suggesting that IL-33 is potentially involved in the pathogenesis of clonorchiasis. However, the roles and potential mechanism of IL-33 underlying remain unknown.
METHODS: Wild-type (WT) and IL-33 knockout (KO) mice (BALB/c female mice) were orally infected with 45 metacercariae of C. sinensis for 8 weeks. Biliary injuries and fibrosis were extensively evaluated. Hepatic type II cytokines (IL-4, IL-13, and IL-10) were detected by ELISA.
RESULTS: For wild-type mice, we found that the mice infected with C. sinensis showed severe biliary injuries and fibrosis compared with the normal mice that were free from worm infection. In addition, the levels of type II cytokines such as IL-4, IL-13, and IL-10 in infected wild-type mice were significantly higher than in the control mice without infection (P < 0.05). However, IL-33 deficiency (IL-33 KO) prevents the augmentation of biliary injuries and fibrosis caused by C. sinensis infection. Furthermore, the increased levels of these type II cytokines induced by worm infection were also reversed in IL-33 KO mice.
CONCLUSIONS: Our present study demonstrates that IL-33 contributes to the pathogenesis of C. sinensis-induced biliary injuries and repair, which can potentially orchestrate type 2 responses. These findings highlight the pathophysiological role of IL-33 in the progression of clonorchiasis.
METHODS: Wild-type (WT) and IL-33 knockout (KO) mice (BALB/c female mice) were orally infected with 45 metacercariae of C. sinensis for 8 weeks. Biliary injuries and fibrosis were extensively evaluated. Hepatic type II cytokines (IL-4, IL-13, and IL-10) were detected by ELISA.
RESULTS: For wild-type mice, we found that the mice infected with C. sinensis showed severe biliary injuries and fibrosis compared with the normal mice that were free from worm infection. In addition, the levels of type II cytokines such as IL-4, IL-13, and IL-10 in infected wild-type mice were significantly higher than in the control mice without infection (P < 0.05). However, IL-33 deficiency (IL-33 KO) prevents the augmentation of biliary injuries and fibrosis caused by C. sinensis infection. Furthermore, the increased levels of these type II cytokines induced by worm infection were also reversed in IL-33 KO mice.
CONCLUSIONS: Our present study demonstrates that IL-33 contributes to the pathogenesis of C. sinensis-induced biliary injuries and repair, which can potentially orchestrate type 2 responses. These findings highlight the pathophysiological role of IL-33 in the progression of clonorchiasis.
摘要：
背景：由华支睾吸虫引起的华支睾吸虫病是一种以胆管炎为特征的人畜共患寄生虫病，胆道增生,胆道纤维化,甚至是胆管癌.我们以前的研究表明，白细胞介素（IL）-33的表达在人类和小鼠感染。提示IL-33可能参与华支睾吸虫病的发病机制。然而,IL-33的作用和潜在机制尚不清楚。
方法:野生型(WT)和IL-33基因敲除(KO)小鼠(BALB/c雌性小鼠)口服感染45只中华毛虫,持续8周。对胆道损伤和纤维化进行了广泛评估。ELISA法检测肝脏II型细胞因子(IL-4、IL-13和IL-10)。
结果：对于野生型小鼠，我们发现，与没有蠕虫感染的正常小鼠相比，感染了C.sinensis的小鼠表现出严重的胆道损伤和纤维化。此外,感染的野生型小鼠的II型细胞因子如IL-4、IL-13和IL-10水平显著高于未感染的对照小鼠(P<0.05)。然而,IL-33缺乏(IL-33KO)可防止由中华梭菌感染引起的胆道损伤和纤维化的增加。此外，由蠕虫感染诱导的这些II型细胞因子水平的升高在IL-33KO小鼠中也被逆转。
结论：我们目前的研究表明，IL-33参与了中华梭菌引起的胆道损伤和修复的发病机制，这可能会协调类型2的响应。这些发现强调了IL-33在华支睾吸虫病进展中的病理生理作用。
方法:野生型(WT)和IL-33基因敲除(KO)小鼠(BALB/c雌性小鼠)口服感染45只中华毛虫,持续8周。对胆道损伤和纤维化进行了广泛评估。ELISA法检测肝脏II型细胞因子(IL-4、IL-13和IL-10)。
结果：对于野生型小鼠，我们发现，与没有蠕虫感染的正常小鼠相比，感染了C.sinensis的小鼠表现出严重的胆道损伤和纤维化。此外,感染的野生型小鼠的II型细胞因子如IL-4、IL-13和IL-10水平显著高于未感染的对照小鼠(P<0.05)。然而,IL-33缺乏(IL-33KO)可防止由中华梭菌感染引起的胆道损伤和纤维化的增加。此外，由蠕虫感染诱导的这些II型细胞因子水平的升高在IL-33KO小鼠中也被逆转。
结论：我们目前的研究表明，IL-33参与了中华梭菌引起的胆道损伤和修复的发病机制，这可能会协调类型2的响应。这些发现强调了IL-33在华支睾吸虫病进展中的病理生理作用。
