Cultured astrocytes express toll‐like receptors for bacterial products

GLIA - Tập 43 Số 3 - Trang 281-291 - 2003
Christal C. Bowman1, Amy Rasley2, Susanne Tranguch2, Ian Marriott2
1Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA
2Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina

Tóm tắt

AbstractIt has become apparent that astrocytes may be important contributors to inflammatory immune responses within the brain in response to microbial challenges. To date, the mechanisms that underlie activation of this major glial cell type by such challenges have not been investigated. In the present study, we present evidence for members of a recently discovered family of receptors for highly conserved microbial components, the Toll‐like receptors (TLRs), in isolated cultures of primary murine astrocytes. We describe the low‐level constitutive expression of messenger RNA‐encoding TLR2, TLR4, TLR5, and TLR9 in resting cultures of these cells. Importantly, the level of expression of messenger RNA for each of these receptors is markedly elevated following exposure to specific bacteria‐derived ligands for these receptors. The functional expression of these receptor proteins is further supported by the ability of known ligands for each TLR to induce both message expression and protein secretion of the proinflammatory cytokine, interleukin‐6. In addition, the recent availability of antibodies to TLR2 and TLR4 has enabled us to demonstrate directly the presence of these receptors on astrocytes by Western blot and immunofluorescence analysis, respectively. Furthermore, we have confirmed the sensitivity of such receptor expression to ligand stimulation. The present demonstration of Toll‐like microbial pattern‐recognition receptors on primary astrocytes provides a mechanistic link between bacterial challenge and inflammatory immune responses that may be an important component of the pathologies of bacterially induced inflammatory CNS disorders. © 2003 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

10.4049/jimmunol.164.7.3471

10.1016/0165-5728(90)90104-U

Cauwels A, 1999, The origin and function of soluble CD14 in experimental bacterial meningitis, J Immunol, 162, 4762, 10.4049/jimmunol.162.8.4762

10.1016/0378-1119(92)90387-5

10.1074/jbc.274.16.10689

10.4049/jimmunol.144.8.2999

10.1128/IAI.64.6.1906-1912.1996

10.1002/glia.1107

10.1074/jbc.273.15.8680

10.1006/cyto.1997.0232

10.1016/0006-8993(94)91233-5

10.1006/bbrc.1998.9378

10.1016/S0006-8993(98)00227-3

10.1038/35074106

10.1038/35047123

10.4049/jimmunol.163.5.2382

Hoshino K, 1999, Toll‐like receptor 4 (TLR4)‐deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product, J Immunol, 162, 3749, 10.4049/jimmunol.162.7.3749

Ibrahim GF, 1985, Method for the isolation of highly purified Salmonella flagellins, J Clin Microbiol, 22, 1040, 10.1128/jcm.22.6.1040-1044.1985

10.4049/jimmunol.165.7.3541

10.3109/08820139509060705

Krueger BK, 1995, Evidence for large‐scale astrocyte death in the developing cerebellum, J Neurosci, 15, 3366, 10.1523/JNEUROSCI.15-05-03366.1995

10.1523/JNEUROSCI.22-07-02478.2002

10.1073/pnas.86.16.6348

10.1172/JCI8541

10.1006/cimm.1998.1248

10.1002/(SICI)1097-4652(199811)177:2<232::AID-JCP5>3.0.CO;2-O

10.4049/jimmunol.165.1.182

10.1016/S0966-842X(00)01845-X

10.1016/S0165-5728(98)00109-X

10.4049/jimmunol.164.7.3476

10.1111/j.1574-695X.2007.00218.x

10.3109/13550289909029749

10.3109/13550289909021287

10.1006/bcmd.1998.0201

10.1016/S0165-5728(02)00187-X

10.1002/glia.10034

10.1016/S0165-5728(00)00428-8

10.1002/(SICI)1098-1136(199803)22:3<295::AID-GLIA8>3.0.CO;2-4

10.1006/geno.2000.6115

10.1016/S0022-510X(02)00005-9

10.4049/jimmunol.168.1.392

10.1097/00001756-200110080-00010

10.1016/S1567-5769(01)00010-8

10.1093/nar/13.7.2485

10.1073/pnas.96.25.14459

10.1002/eji.1830180202

10.1097/00019052-200106000-00018

10.1042/bj3130519

10.4049/jimmunol.168.1.348

10.1084/jem.189.4.605

Yoshimura A, 1999, Recognition of Gram‐positive bacterial cell wall components by the innate immune system occurs via Toll‐like receptor 2, J Immunol, 163, 1, 10.4049/jimmunol.163.1.1

Thông tin
Thông tin xuất bản

GLIA

Tập 43 Số 3

281-291

Thông tin tác giả