Nitric oxide-enhanced resistance to oral candidiasis

Nitric oxide-enhanced resistance to oral candidiasis
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DOI:
10.1046/j.1365-2567.2001.01331.x
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发表时间:
2001-12-01
期刊:
影响因子:
6.4
通讯作者:
Clancy, R
Clancy, R
中科院分区:
医学2区
文献类型:
--
作者:
Elahi, S;Pang, G;Clancy, R

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一种海洋口腔念珠菌病模型被用来证明一氧化氮(NO)参与宿主抵抗感染白色念珠菌的BALB/c和易感染的DBA/2小鼠。感染后,唾液中的NO生成量增加。感染后唾液样品在体外对酵母菌的生长有抑制作用。用NO合成抑制剂N-G-单甲基-L-精氨酸处理后,NO产量减少,这与白色念珠菌的生长增加有关。MMLA治疗后NO产量的减少与区域淋巴结细胞中白细胞介素4(IL-4)的减少有关,而与干扰素-γ(干扰素-γ)的基因表达无关。在易感染的DBA/2小鼠中,IL-4的产生下调伴随着干扰素-γ的产生的增加。抗IL-4单抗处理的小鼠唾液和C-白色念珠菌抗原刺激的颈淋巴细胞培养中NO的产生明显受到抑制,表明IL-4与NO的产生有一定的功能关系。这些结果支持了以前的结论,即IL-4与口腔念珠菌病的耐药性有关,并提示NO参与控制口腔黏膜表面白色念珠菌的定植。
A marine model of oral candidiasis was used to show that nitric oxide (NO) is involved in host resistance to infection with Candida albicans in infection-'resistant' BALB/c and infection-'prone' DBA/2 mice. Following infection, increased NO production was detected in saliva. Postinfection samples of saliva inhibited the growth of yeast in vitro. Treatment with N-G-monomethyl-L-arginine (MMLA), an inhibitor of NO synthesis, led to reduced NO production, which correlated with an increase in C. albicans growth. Reduction in NO production following MMLA treatment correlated with an abrogation of interleukin-4 (IL-4), but not interferon-gamma (IFN-gamma), mRNA gene expression in regional lymph node cells. Down-regulation of IL-4 production was accompanied with an increase in IFN-gamma production in infection-'prone' DBA/2 mice. There was a functional relationship between IL-4 and NO production in that mice treated with anti-IL-4 monoclonal antibody showed a marked inhibition of NO production in saliva and in culture of cervical lymph node cells stimulated with C albicans antigen. The results Support previous conclusions that IL-4 is associated with resistance to oral candidiasis and suggest that NO is involved in controlling colonization of the oral mucosal surface with C albicans.