Leishmania (L.) amazonensis-induced inhibition of nitric oxide synthesis in host macrophages
Leishmania (L.) amazonensis-induced inhibition of nitric oxide synthesis in host macrophages
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DOI：
10.1016/s1286-4579(01)01505-2
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发表时间：
2002-01-01
影响因子：
5.8
通讯作者：
Abrahamsohn, ID
中科院分区：
文献类型：
--
作者：
Balestieri, FMP;Queiroz, ARP;Abrahamsohn, ID
在感染亚马逊利什曼原虫的J774-G8巨噬细胞中，证实了脂多糖（LPS）诱导的一氧化氮（NO）产生的抑制作用。在感染和lps刺激的J774-G8细胞中观察到NO产生的下调与诱导型一氧化氮合酶（iNOS）活性的降低相关。iNOS活性的降低与iNOS mRNA表达的降低并不平行，这表明寄生虫影响了NO合成的转录后事件。补充l -精氨酸或四氢生物蝶呤并没有增加NO的产生，这表明抑制不是由于底物或辅助因子的不足，用抗il -10、抗il -4或抗tgf - β中和抗体治疗也未能增加NO的产生，这表明这些细胞因子与观察到的寄生虫诱导的NO合成抑制无关。然而，用ifn - γ处理培养物导致受感染的lps刺激的细胞产生NO的显著增加。上述结果表明，虽然亚马逊乳杆菌感染抑制了J774-G8细胞的iNOS活性和NO的产生，但ifn - γ的激活能够超越对NO合成的抑制。(C) 2002年版《科学与医学》Elsevier SAS。版权所有。
Inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production was demonstrated in J774-G8 macrophages infected with Leishmania (L.) amazonensis promastigotes. The downmodulation of NO production observed in infected and LPS-stimulated J774-G8 cells correlated with a reduction in inducible nitric oxide synthase (iNOS) activity. Reduction in iNOS activity was not paralleled by decreased iNOS mRNA expression, suggesting that the parasite affects post-transcriptional events of NO synthesis. Supplementation with L-arginine or tetrahydrobiopterin did not increase NO production, suggesting that inhibition is not due to an insufficiency of substrate or co-factor, Treatment with anti-IL-10, anti-IL-4 or anti-TGF-beta neutralizing antibodies also failed to increase NO production, indicating that these cytokines are not involved in the observed parasite-induced inhibition of NO synthesis. However, treatment of the cultures with IFN-gamma resulted in a marked increase in NO production by infected LPS-stimulated cells. These results show that although L.(L.) amazonensis infection inhibits iNOS activity and NO production by J774-G8 cells, activation by IFN-gamma is capable of overriding the suppression of NO synthesis. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.