Cell activation by Porphyromonas gingivalis lipid A molecule through Toll-like receptor 4-and myeloid differentiation factor 88-dependent signaling pathway

被引:106
作者
Ogawa, T
Asai, Y
Hashimoto, M
Takeuchi, O
Kurita, T
Yoshikai, Y
Miyake, K
Akira, S
机构
[1] Asahi Univ, Sch Dent, Dept Oral Microbiol, Gifu, Japan
[2] Osaka Univ, Res Inst Microbial Dis, Dept Host Def, Suita, Osaka 5650871, Japan
[3] Nihon Univ, Sch Dent MMatsudo, Dept Microbiol, Chiba 2718587, Japan
[4] Kyushu Univ, Div Host Def, Res Ctr Prevent Infect Dis, Med Inst Bioregulat, Fukuoka 8128582, Japan
[5] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Infect Genet, Tokyo 1088639, Japan
关键词
lipid A; lipopolysaccharide; periodontal disease; Porphyromonas gingivalis; Toll-like receptor;
D O I
10.1093/intimm/dxf097
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Porphyromonas gingivalis lipopolysaccharide (LPS) and its bioactive center, lipid A, are known to exhibit very low endotoxic activities and activate LPS-hyporesponsive C3H/HeJ mice that have a point mutation in the cytoplasmic portion of Toll-like receptor (TLR) 4, in contrast to classical enterobacterial LPS and their lipid A. In the present study, we attempted to determine which TLR mediates the response to lipid A from P. gingivalis strain 381. P. gingivalis LPS and its natural lipid A fraction induced NF-kappaB activation primarily in Ba/F3 cells expressing mouse TLR 2 (Ba/mTLR2), rather than in those expressing mouse TLR4 and its accessory protein MD2 (Ba/mTLR4/mMD2). Further purification of the natural lipid A fraction resulted in a significant decrease of NF-kappaB activation in Ba/mTLR2, although not in Ba/mTLR4/mMD2. The synthetic counterpart of P. gingivalis strain 381-lipid A (compound PG-381) also elicited NF-kappaB activation in Ba/mTLR4/mMD2, but not Ba/mTLR2. Furthermore, P. gingivalis purified natural lipid A and compound PG-381 lacked the ability to activate gingival fibroblasts from C3H/HeJ, TLR4 knockout (KO) and myeloid differentiation factor 88 (MyD88) KO mice. These findings demonstrate that the P. gingivalis lipid A molecule induces cell activation via a TLR4/MD2-MyD88-dependent pathway, and suggest the possibility that unknown bacterial components in P. gingivalis LPS and its lipid A may induce cell activation via TLR2.
引用
收藏
页码:1325 / 1332
页数:8
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