Profile of Toll-like receptor expressions and induction of nitric oxide synthesis by Toll-like receptor agonists in chicken monocytes

Profile of Toll-like receptor expressions and induction of nitric oxide synthesis by Toll-like receptor agonists in chicken monocytes
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DOI:
10.1016/j.molimm.2005.07.002
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发表时间:
2006-03-01
影响因子:
3.6
通讯作者:
Kogut, MH
Kogut, MH
中科院分区:
医学3区
文献类型:
--
作者:
He, HQ;Genovese, KJ;Kogut, MH

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Toll样受体(TLR)在先天免疫系统中起主要作用,用于初始识别微生物病原体和病原体相关组分。一氧化氮(NO)是免疫细胞对微生物刺激的反应,参与感染的发病机制和控制。我们使用RT-PCR分析来检查鸡单核细胞上的TLR表达谱,并证明这些细胞表达鸡TLR 2、3、4、6和7。TR-PCR未检测到TLR 5。我们还研究了TLR激动剂对鸡单核细胞NO合成的差异诱导作用,包括鞭毛蛋白(FGN,来自鼠伤寒沙门氏菌)、合成脂蛋白Pam 3CSK 4(PAM)、脂多糖(LPS,来自沙门氏菌)、脂磷壁酸(LTA)。来自金黄色葡萄球菌)、合成的双链RNA类似物(聚I:C)、鸟苷类似物、洛索立宾(LOX)和合成的CpG寡脱氧二核苷酸(CpG-ODN)。我们的研究结果表明,这些激动剂诱导NO产生的能力有很大的差异。CpG-ODN和LPS是最有效的刺激,并诱导显着数量的NO在培养的单核细胞,而LTA刺激显着的NO生产只有在高浓度。其他激动剂如FGN和Poly I:C刺激非常少的NO,而PAM、LOX和nCpG-ODN(对照ODN)不诱导NO产生。RT-PCR分析表明,LPS,LTA,和CpG-ODN诱导单核细胞诱导型一氧化氮合酶(iNOS)的表达,而其他激动剂没有。鸡单核细胞上TLR的存在和各种TLR激动剂对鸡单核细胞中NO产生的差异诱导表明单个TLR下游的信号传导途径的分化。(C)2005爱思唯尔有限公司保留所有权利。
Toll-like receptors (TLRs) play a major role in the innate immune system for initial recognition of microbial pathogens and pathogen associated components. Nitric oxide (NO) is generated in immune cells in response to microbial Stimulation and is involved in pathogenesis and control of infection. We used RT-PCR analysis to examine the TLR expression profile on chicken monocytes and demonstrated these cells express chicken TLR2, 3, 4, 6, and 7. TLR5 was not detected by the TR-PCR. We also investigated the differential induction of NO synthesis in chicken monocytes by TLR agonists, including flagellin (FGN, from Salmonella typhimurium), synthetic lipoprotein Pam3CSK4 (PAM), lipopolysaccharide (LPS, from Salmonella enteritidis), lipoteichoic acid (LTA. from Staphylococcus aureus), the synthetic double stranded RNA analog (poly I:C), the guanosine analog, loxoribine (LOX), and synthetic CpG oligodeoxydinucleotide (CpG-ODN). Our results indicate that there was a vast difference among these agonists for their ability to induce NO production. CpG-ODN and LPS were the most potent stimuli and induced significant quantities of NO in cultured monocytes, whereas LTA stimulated significant NO production only at high concentrations. Other agonists such as FGN and Poly I:C stimulated very little NO, while PAM, LOX, and nCpG-ODN (control ODN) did not induce NO production. RT-PCR analysis demonstrated that LPS, LTA, and CpG-ODN induced inducible nitric oxide synthase (iNOS) expression in monocytes; whereas the other agonists did not. The presence of TLRs on chicken monocytes and the differential induction of NO production in chicken monocytes by various TLR agonists Suggest the differentiation of signaling pathways downstream of individual TLRs. (C) 2005 Elsevier Ltd. All rights reserved.