Negative regulation of Schistosoma japonicum egg-induced liver fibrosis by natural killer cells.

Negative regulation of Schistosoma japonicum egg-induced liver fibrosis by natural killer cells.
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自然杀伤细胞对日本血吸虫虫卵所致肝纤维化的负调控

DOI:
10.1371/journal.pntd.0001456
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发表时间:
2012-01
影响因子:
3.8
通讯作者:
Shen J
Shen J
中科院分区:
医学2区
文献类型:
--
作者:
Hou X;Yu F;Man S;Huang D;Zhang Y;Liu M;Ren C;Shen J

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自然杀伤(NK)细胞在感染诱导的肝纤维化中的作用仍不清楚。本研究旨在阐明NK细胞对日本血吸虫的作用。鸡胚肝纤维化。用18-20条血吸虫尾蚴感染C57 BL/6小鼠,诱导肝纤维化。山茱萸使用抗ASGM 1抗体耗竭NK细胞。Toll样受体3配体聚肌苷酸-聚胞苷酸(poly I∶C)可增强NK细胞的活化。结果表明,S.日本血吸虫感染,如通过CD 69表达和IFN-γ产生的升高所证明的。NK细胞的耗竭显著增强了S.鸡胚肝纤维化。poly I∶C进一步激活NK细胞产生IFN-γ和减毒的S.鸡胚肝纤维化。观察到的PolyI ∶C对肝纤维化的保护作用通过耗尽NK细胞而减弱。干扰素-γ基因的破坏可增强肝纤维化,并部分取消聚I∶C对肝纤维化的抑制作用。此外,在活化的肝星状细胞中,可检测到NKG 2D配体视黄酸早期诱导因子1(RAE 1)的高水平表达。日本血吸虫感染的小鼠,这使它们更容易受到肝脏NK细胞杀伤。总之,我们的研究结果表明,在S。日本血吸虫感染通过产生IFN-γ和杀死活化星状细胞负性调节鸡蛋诱导的肝纤维化。
The role of natural killer (NK) cells in infection-induced liver fibrosis remains obscure. In this study, we elucidated the effect of NK cells on Schistosoma japonicum (S. japonicum) egg-induced liver fibrosis. Liver fibrosis was induced by infecting C57BL/6 mice with 18–20 cercariae of S. japonicum. Anti-ASGM1 antibody was used to deplete NK cells. Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid (poly I∶C) was used to enhance the activation of NK cells. Results showed that NK cells were accumulated and activated after S. japonicum infection, as evidenced by the elevation of CD69 expression and IFN-γ production. Depletion of NK cells markedly enhanced S. japonicum egg-induced liver fibrosis. Administration of poly I∶C further activated NK cells to produce IFN-γ and attenuated S. japonicum egg-induced liver fibrosis. The observed protective effect of poly I∶C on liver fibrosis was diminished through depletion of NK cells. Disruption of IFN-γ gene enhanced liver fibrosis and partially abolished the suppression of liver fibrosis by poly I∶C. Moreover, expression of retinoic acid early inducible 1 (RAE 1), the NKG2D ligand, was detectable at high levels on activated hepatic stellate cells derived from S. japonicum-infected mice, which made them more susceptible to hepatic NK cell killing. In conclusion, our findings suggest that the activated NK cells in the liver after S. japonicum infection negatively regulate egg-induced liver fibrosis via producing IFN-γ, and killing activated stellate cells.
DOI: 10.1016/s0168-8278(97)80258-9
发表时间: 1997-04-01
影响因子: 25.7
作者:
Lortat-Jacob, H;Baltzer, F;Grimaud, JA
通讯作者: Grimaud, JA
DOI: 10.1016/j.biocel.2008.05.001
发表时间: 2008-01-01
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作者:
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通讯作者: Tomasello, Elena
DOI: 10.1002/hep.1840100508
发表时间: 1989-11-01
期刊: HEPATOLOGY
影响因子: 13.5
作者:
CZAJA, MJ;WEINER, FR;ZERN, MA
通讯作者: ZERN, MA
DOI: 10.1016/s0165-2478(96)02634-x
发表时间: 1996-12-01
期刊: IMMUNOLOGY LETTERS
影响因子: 4.4
作者:
Asseman, C;Pancre, V;Auriault, C
通讯作者: Auriault, C
DOI: 10.1111/j.1365-3024.1995.tb00972.x
发表时间: 1995-02-01
影响因子: 2.2
作者:
CHEEVER, AW;FINKELMAN, FD;COX, TM
通讯作者: COX, TM