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Comparison of the neuroinflammatory pathways induced by TLR7, TLR8 and TLR9 agonists in the neonatal brain
Author(s) -
Butchi Niranjan Babu,
Pourciau Susan,
Du Min,
Morgan Timothy,
Peterson Karin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.672.46
Subject(s) - tlr7 , neuroinflammation , tlr9 , stimulation , astrocyte , receptor , agonist , neuroscience , biology , central nervous system , immune system , immunology , innate immune system , toll like receptor , inflammation , gene expression , biochemistry , dna methylation , gene
Neuroinflammation in the central nervous system is a common finding in a variety of neurological diseases induced by viruses, bacteria and injury as well as those of unclear etiologies. The TLR9 family members are strong candidates for regulating neuroinflammatory responses as ligands for these receptors are expressed by a number of pathogens that can infect the CNS and induce neuronal damage. To examine the potential role of TLR7, 8 and 9 in glia activation, neuroinflammation and neuronal damage, a single inoculum of Imiquimod, 3M002 or CpG DNA respectively were injected intracerebrally into new born mice. TLR9 stimulation induced a stronger neuroinflammatory response as compared to either TLR7 or TLR8 stimulation, despite the use of much lower molar dose of TLR9 agonist. In addition, we analyzed the influence of one TLR stimulation on the expression of other TLRs in neonatal brain in vivo and in astrocyte and mixed glia cultures ex vivo. Our preliminary results indicate that TLR7 stimulation alters the expression of TLR8 and 9, but not TLR7. Stimulation of TLR9 alters expression of TLR8. As these receptors have been shown to interact with each other's signaling, the alteration of TLR expression may have auto‐regulatory functions. We are currently analyzing the interaction between these receptors in neuroinflammation utilizing TLR7 and TLR9 deficient mice. This research is supported by NCRR # 1P20RR20159‐01.