Vascular dysfunction following polymicrobial sepsis: role of pattern recognition receptors.
Vascular dysfunction following polymicrobial sepsis: role of pattern recognition receptors.
复制标题
DOI：
10.1371/journal.pone.0044531
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Meyer R
中科院分区：
文献类型：
--
作者：
Ehrentraut SF;Dörr A;Ehrentraut H;Lohner R;Lee SH;Hoeft A;Baumgarten G;Knuefermann P;Boehm O;Meyer R
目的是阐明模式识别受体在多微生物败血症（升结肠支架腹膜炎，CASP）血管功能障碍中的特定作用。在CASP后18小时测量C57 BL/6（野生型）小鼠和Toll样受体2/4/9（TLR 2-D、TLR 4-D、TLR 9-D）或CD 14（CD 14-D）缺陷的小鼠的血管收缩性。采用RT-qPCR法测定肿瘤坏死因子-α（TNFα）、白细胞介素（IL）-1β、IL-6、抗炎细胞因子（IL-10）和血管诱导型一氧化氮合酶（iNOS）的mRNA表达。野生型小鼠在CASP后表现出显著的血管收缩性损失。这在TLR 2-D小鼠中加重，在TLR 4-D动物中减弱，在TLR 9-D和CD 14-D动物中消除。在野生型和TLR 2-D动物中，CASP后TNF-α表达显著上调，但在TLR 4、TLR 9或CD 14缺陷的小鼠中没有。iNOS仅在TLR 2-D动物中显著上调。TLR 2-D动物显示显著更高水平的TLR 4、TLR 9和CD 14。TLR 9拮抗剂H154-ODN的应用减轻了CASP诱导的野生型小鼠细胞因子释放和血管功能障碍。在我们的模型中，CD 14和TLR 9在血管功能障碍的发展中起决定性作用，因此可以使用H154-ODN有效拮抗。TLR 2-D动物更容易发生多微生物败血症，可能是由于TLR 4、9和CD 14的上调。
Aim was to elucidate the specific role of pattern recognition receptors in vascular dysfunction during polymicrobial sepsis (colon ascendens stent peritonitis, CASP). Vascular contractility of C57BL/6 (wildtype) mice and mice deficient for Toll-like receptor 2/4/9 (TLR2-D, TLR4-D, TLR9-D) or CD14 (CD14-D) was measured 18 h following CASP. mRNA expression of pro- (Tumor Necrosis Factor-α (TNFα), Interleukin (IL)-1β, IL-6) and anti-inflammatory cytokines (IL-10) and of vascular inducible NO-Synthase (iNOS) was determined using RT-qPCR. Wildtype mice exhibited a significant loss of vascular contractility after CASP. This was aggravated in TLR2-D mice, blunted in TLR4-D animals and abolished in TLR9-D and CD14-D animals. TNF-α expression was significantly up-regulated after CASP in wildtype and TLR2-D animals, but not in mice deficient for TLR4, -9 or CD14. iNOS was significantly up-regulated in TLR2-D animals only. TLR2-D animals showed significantly higher levels of TLR4, -9 and CD14. Application of H154-ODN, a TLR9 antagonist, attenuated CASP-induced cytokine release and vascular dysfunction in wildtype mice. Within our model, CD14 and TLR9 play a decisive role for the development of vascular dysfunction and thus can be effectively antagonized using H154-ODN. TLR2-D animals are more prone to polymicrobial sepsis, presumably due to up-regulation of TLR4, 9 and CD14.
登录
查看更多内容
影响因子：
37.8
作者：
Grandel, U;Fink, L;Sibelius, U
通讯作者：
Sibelius, U
影响因子：
6.4
作者：
Echchannaoui, H;Frei, K;Landmann, R
通讯作者：
Landmann, R
影响因子：
15.9
作者：
Lien, E;Means, TK;Golenbock, DT
通讯作者：
Golenbock, DT
影响因子：
3.1
作者：
Ehrentraut, Stefan;Lohner, Ralph;Knuefermann, Pascal
通讯作者：
Knuefermann, Pascal
影响因子：
37.8
作者：
Knuefermann, P;Nemoto, S;Vallejo, JG
通讯作者：
Vallejo, JG