Direct binding of toll-like receptor 2 to zymosan, and zymosan-induced NF-κB activation and TNF-α secretion are down-regulated by lung collectin surfactant protein A

被引:298
作者
Sato, M
Sano, H
Iwaki, D
Kudo, K
Konishi, M
Takahashi, H
Takahashi, T
Imaizumi, H
Asai, Y
Kuroki, Y
机构
[1] Sapporo Med Univ, Sch Med, Dept Biochem, Chuo Ku, Sapporo, Hokkaido 0608556, Japan
[2] Sapporo Med Univ, Sch Med, Dept Traumatol & Crit Care Med, Chuo Ku, Sapporo, Hokkaido 0608556, Japan
[3] Sapporo Med Univ, Sch Med, Dept Internal Med 3, Chuo Ku, Sapporo, Hokkaido 0608556, Japan
关键词
D O I
10.4049/jimmunol.171.1.417
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The lung collectin surfactant protein A (SP-A) has been implicated in the regulation of pulmonary host defense and inflammation. Zymosan induces proinflammatory cytokines in immune cells. Toll-like receptor (TLR)2 has been shown to be involved in zymosan-induced signaling. We first investigated the interaction of TLR2 with zymosan. Zymosan cosedimented the soluble form of rTLR2 possessing the putative extracellular domain (sTLR2). sTLR2 directly bound to zymosan with an apparent binding constant of 48 nM. We next examined whether SP-A modulated zymosan-induced cellular responses. SP-A significantly attenuated zymosan-induced TNF-alpha secretion in RAW264.7 cells and alveolar macrophages in a concentration-dependent manner. Although zymosan failed to cosediment SP-A, SP-A significantly reduced zymosan-elicited NF-kappaB activation in TLR2-transfected human embryonic kidney 293 cells. Because we have shown that SP-A binds to sTLR2, we also examined whether SP-A affected the binding of sTLR2 to zymosan. SP-A significantly attenuated the direct binding of sTLR2 to zymosan in a concentration-dependent fashion. From these results, we conclude that 1) TLR2 directly binds zymosan, 2) SP-A can alter zymosan-TLR2 interaction, and 3) SP-A down-regulates TLR2-mediated signaling and TNF-a secretion stimulated by zymosan. This study supports an important role of SP-A in controlling. pulmonary inflammation caused by microbial pathogens.
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页码:417 / 425
页数:9
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