Identification of soluble CD14 as an endogenous agonist for Toll‐like receptor 2 on human astrocytes by genome‐scale functional screening of glial cell derived proteins

GLIA - Tập 55 Số 5 - Trang 473-482 - 2007
Malika Bsibsi1, Jeffrey J. Bajramović2, Eveline van Duijvenvoorden1, Carla Persoon1, Rivka Ravid3, Johannes M. van Noort1, Mario H. J. Vogt4
1Department of Biosciences, TNO Quality of Life, Leiden, The Netherlands
2Unit Alternatives, Biomedical Primate Research Centre, Rijswijk, The Netherlands
3Netherlands Brain Bank, Amsterdam, The Netherlands
4Department of Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, The Netherlands

Tóm tắt

AbstractHuman astrocytes express a limited repertoire of Toll‐like receptor (TLR) family members including TLR1‐4, which are expressed on the cell surface. Also, TLR3 but not TLR4 activation on astrocytes induces expression of several factors involved in neuroprotection and down‐regulation of inflammation rather than in the onset of traditional pro‐inflammatory reactions. The notion that astrocyte TLR may thus play a role not only in host defense but also in tissue repair responses prompted us to examine the possibility that endogenous TLR agonists could be expressed in the human central nervous system to regulate the apparently dual astrocyte functions during trauma or inflammation. As a potential source of endogenous agonists, a cDNA library derived from several human brain tumor cell lines was used. Gene pools of this library were transfected into COS‐7 cells and the expression products were screened for their ability to induce TLR activation in human primary astrocytes. The screening resulted in the identification of soluble CD14. By using a panel of TLR‐transfected HEK293 cells, we found that signaling by soluble CD14 was TLR2 dependent. Moreover, the CD14‐triggered TLR2‐mediated response in astrocytes lead to the production of CXCL8, IL‐6, and IL12p40, whereas typical TLR‐induced pro‐inflammatory cytokines, like TNF‐α and IL‐1β, were not produced at detectable levels. In conclusion, our data indicate that apart from its well‐known ability to act as a co‐receptor for TLR‐dependent signaling by peptidoglycans or LPS, soluble CD14 can also act as a direct agonist for TLR2. © 2007 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1042/BST0310637

10.1084/jem.20050914

10.1016/j.molimm.2003.10.005

10.1002/glia.20328

10.1093/jnen/61.11.1013

10.2165/00003495-200666010-00002

10.1038/nature01355

10.1002/jemt.1118

10.1006/jmbi.2000.3903

10.1046/j.1471-4159.2003.02202.x

10.4049/jimmunol.176.11.6491

10.4049/jimmunol.164.4.2064

10.1016/S1471-4906(02)00014-5

10.1128/IAI.66.5.2264-2271.1998

10.1084/jem.20050630

10.1086/315357

10.1002/eji.200425336

10.1038/sj.onc.1206406

10.1038/nbt746

10.4049/jimmunol.177.1.322

10.1016/j.jim.2005.07.026

10.1111/j.0105-2896.2005.00239.x

10.4049/jimmunol.176.11.7021

10.1093/intimm/13.7.933

10.4049/jimmunol.169.1.10

10.1177/09680519000060060201

10.1159/000092078

10.1189/jlb.0205064

10.1016/j.virol.2006.04.029

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GLIA

Tập 55 Số 5

473-482

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