Cultured astrocytes express toll‐like receptors for bacterial products
Tóm tắt
It 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
Cauwels A, 1999, The origin and function of soluble CD14 in experimental bacterial meningitis, J Immunol, 162, 4762, 10.4049/jimmunol.162.8.4762
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
Krueger BK, 1995, Evidence for large‐scale astrocyte death in the developing cerebellum, J Neurosci, 15, 3366, 10.1523/JNEUROSCI.15-05-03366.1995