Signal integration in lipopolysaccharide (LPS)-stimulated murine macrophages

Signal integration in lipopolysaccharide (LPS)-stimulated murine macrophages
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脂多糖 (LPS) 刺激的小鼠巨噬细胞中的信号整合

DOI:
10.1177/09680519010070030801
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发表时间:
2001
期刊:
Journal of Endotoxin Research
影响因子:
--
通讯作者:
P. Perera
P. Perera
中科院分区:
--
文献类型:
--
作者:
S. Vogel;Matthew J. Hirschfeld;P. Perera

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使用一组 LPS 诱导基因(根据其产物产生内毒性的能力进行选择),将正常巨噬细胞与缺乏 CD14、CD11b/CD18 或 TLR4 的巨噬细胞进行比较,以诱导响应大肠杆菌 LPS 或 LPS 模拟物紫杉醇的基因表达。所有基因均依赖于 TLR4。在低剂量的 LPS 或紫杉醇下,所有基因也都是 CD14 依赖性的;然而,即使在高得多的浓度下,IP-10 和 ICSBP 的诱导性仍然很差。一个独特的基因子集(COX-2、IL-12 p40 和 IL-12 p35)是 CD11b/CD18 依赖性的。受体缺陷型巨噬细胞中 NF-κB 易位和 MAPK 磷酸化失调。与大肠杆菌 LPS 相比,牙龈卟啉单胞菌 LPS 制剂被发现是 TLR2 依赖性的,而不是 TLR4 依赖性的,并导致组内基因的差异表达。这些数据表明:(i)TLR4对于诱导所检查的全部基因是必要的,但还不够; (ii) CD14和CD11b/CD18促进信号传导,以诱导也依赖于TLR4的选定基因子集; (iii) 通过 TLR2 与 TLR4 的信号传导在数量/质量上有所不同。这些数据支持小鼠巨噬细胞上的 LPS 信号复合物,该复合物至少包括 CD14、CD11b/CD18 和 TLR4,以响应大肠杆菌 LPS,从而引发全谱基因表达。
Using a panel of LPS-inducible genes, selected for the capacity of their products to contribute to endotoxicity, normal macrophages were compared to macrophages deficient in CD14, CD11b/CD18, or TLR4 to elicit gene expression in response to Escherichia coli LPS or the LPS mimetic, Taxol. All genes were TLR4-dependent. At low doses of LPS or Taxol, all genes were also CD14-dependent; however, IP-10 and ICSBP remained poorly inducible even at much higher concentrations. A distinct subset of genes (COX-2, IL-12 p40, and IL-12 p35) was CD11b/CD18-dependent. NF-κB translocation and MAPK phosphorylation were dysregulated in receptor-deficient macrophages. In contrast to E. coli LPS, a Porphyromonas gingivalis LPS preparation was found to be TLR2-, rather than TLR4-dependent, and resulted in differential expression of genes within the panel. These data suggest that: (i) TLR4 is necessary, but not sufficient, to induce the full repertoire of genes examined; (ii) CD14 and CD11b/CD18 facilitate signaling for induction of select subsets of genes that are also TLR4-dependent; and (iii) signaling through TLR2 versus TLR4 differs quantitatively/qualitatively. These data support an LPS signaling complex on murine macrophages that minimally includes CD14, CD11b/CD18, and TLR4 to respond to E. coli LPS to elicit the full spectrum of gene expression.
来自正常小鼠和用 LPS 或紫杉醇刺激的 CD14“敲除”(CD14KO) 小鼠的小鼠巨噬细胞中 CD14 依赖性和独立信号通路。
DOI: --
发表时间: 1998
期刊: Progress in clinical and biological research
影响因子: --
作者:
Vogel,SN;Perera,PY;Detore,GR;Bhat,N;Carboni,JM;Haziot,A;Goyert,SM
通讯作者: Goyert,SM
DOI: 10.4049/jimmunol.162.12.7335
发表时间: 1999-06
影响因子: 4.4
作者:
N. Bhat;P. Perera;J. Carboni;J. Blanco;D. Golenbock;T. Mayadas;S. Vogel
通讯作者: N. Bhat;P. Perera;J. Carboni;J. Blanco;D. Golenbock;T. Mayadas;S. Vogel
内毒素诱导 C3H/HeJ (Lpsd) 巨噬细胞的早期基因表达。
DOI: --
发表时间: 1994
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Manthey,CL;Perera,PY;Henricson,BE;Hamilton,TA;Qureshi,N;Vogel,SN
通讯作者: Vogel,SN
DOI: 10.1016/s1074-7613(00)80254-x
发表时间: 1996-04-01
期刊: IMMUNITY
影响因子: 32.4
作者:
Haziot, A;Ferrero, E;Goyert, SM
通讯作者: Goyert, SM
DOI: 10.1016/s1074-7613(00)80278-2
发表时间: 1996-12-01
期刊: IMMUNITY
影响因子: 32.4
作者:
Coxon, A;Rieu, P;Mayadas, TN
通讯作者: Mayadas, TN