Chemically synthesized pathogen-associated molecular patterns increase the expression of peptidoglycan recognition proteins via Toll-like receptors, NOD1 and NOD2 in human oral epithelial cells
Chemically synthesized pathogen-associated molecular patterns increase the expression of peptidoglycan recognition proteins via Toll-like receptors, NOD1 and NOD2 in human oral epithelial cells
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DOI：
10.1111/j.1462-5822.2004.00500.x
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发表时间：
2005-05-01
影响因子：
3.4
通讯作者：
Takada, H
中科院分区：
文献类型：
--
作者：
Uehara, A;Sugawara, Y;Takada, H
肽聚糖识别蛋白（PGRPs）是一个新的模式识别分子家族，能识别细菌细胞壁肽聚糖（PGN），具有抗菌活性。在人类中，已经克隆了四种PGRPs（PGRP-L、-I α、-I β和-S），并且所有四种人类PGRPs都结合PGN。在这项研究中，我们研究了在细菌细胞表面成分中化学合成的病原体相关分子模式（PAMPs）：大肠杆菌型三酰基脂肽（Pam 3CSSNA）、大肠杆菌型三酰基脂肽（Escherichia coli type tryacyl lipopeptide，E. coli）、大肠杆菌型三酰基脂肽（E. coli type tryacyl lipopeptide，E. coli）和大肠杆菌型三酰基脂肽（E. coli type tryacyl lipopeptide，E. coli）刺激下，口腔上皮细胞PGRP表达的可能调控。大肠杆菌型脂质A（LA-15-PP）、含二氨基庚二酸的去胞壁酰肽（γ-d-谷氨酰-meso-DAP; iE-DAP）和胞壁酰二肽（MDP）。这些合成的PAMPs显著上调口腔上皮细胞中4种PGRP的mRNA表达和PGRP-1 α和-I β的细胞表面表达，但不诱导mRNA表达或炎性细胞因子的分泌。通过RNA干扰抑制Toll样受体（TLR）2、TLR 4、核苷酸结合寡聚化结构域（NOD）1和NOD 2的表达，可特异性抑制Pam 3CSSNA、LA-15-PP、iE-DAP和MDP诱导的PGRP mRNA表达上调。这些PAMPs肯定激活了上皮细胞中的核因子（NF）-κ B，抑制NF-κ B激活明显阻止了这些PAMPs诱导的PGRP mRNA表达。这些结果表明，细菌PAMPs诱导口腔上皮细胞表达PGRP，而不是促炎细胞因子，PGRP可能参与宿主防御细菌入侵，而不伴随炎症反应。
Peptidoglycan recognition proteins (PGRPs), a novel family of pattern recognition molecules (PRMs) in innate immunity conserved from insects to mammals, recognize bacterial cell wall peptidoglycan (PGN) and are suggested to act as anti-bacterial factors. In humans, four kinds of PGRPs (PGRP-L, -I alpha, -I beta and -S) have been cloned and all four human PGRPs bind PGN. In this study, we examined the possible regulation of the expression of PGRPs in oral epithelial cells upon stimulation with chemically synthesized pathogen-associated molecular patterns (PAMPs) in bacterial cell surface components: Escherichia coli-type tryacyl lipopeptide (Pam3CSSNA), E. coli-type lipid A (LA-15-PP), diaminopimelic acid containing desmuramyl peptide (gamma- d-glutamyl-meso-DAP; iE-DAP), and muramyldipeptide (MDP). These synthetic PAMPs markedly upregulated the mRNA expression of the four PGRPs and cell surface expression of PGRP-I alpha and -I beta, but did not induce either mRNA expression or secretion of inflammatory cytokines, in oral epithelial cells. Suppression of the expression of Toll-like receptor (TLR)2, TLR4, nucleotide-binding oligomerization domain (NOD)1 and NOD2 by RNA interference specifically inhibited the upregulation of PGRP mRNA expression induced by Pam3CSSNA, LA-15-PP, iE-DAP and MDP respectively. These PAMPs definitely activated nuclear factor (NF)-kappa B in the epithelial cells, and suppression of NF-kappa B activation clearly prevented the induction of PGRP mRNA expression induced by these PAMPs in the cells. These findings suggested that bacterial PAMPs induced the expression of PGRPs, but not proinflammatory cytokines, in oral epithelial cells, and the PGRPs might be involved in host defence against bacterial invasion without accompanying inflammatory responses.