TLRシグナルと歯周病
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概要
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Toll-like receptors (TLRs) are a family of mammalian proteins homologous to Drosophila Toll, which was first identified as a protein controlling dorso-ventral pattern formation in the early development. TLR structure is characterized by proline-rich repeats (PRRs) in the extracellular domain and Toll/IL-1 receptor (TIR) motif in the cytoplasmic domain. Each TLR is essential for the recognition of specific pathogen-associated molecular patterns (PAMPs). Among TLRs, TLR4 is essential for LPS responsiveness, and TLR2 is a receptor for bacterial lipoproteins and peptidoglycan. Although TLRs share many downstream signaling molecules, various reports have also suggested differences among the biological responses induced by TLRs. We have recently found that JNK-interacting protein (JIP) 3, a scaffold protein of JNK and its upstream kinases, associates with TLR4 and enhances LPS-mediated JNK activation. As TLR signals (such as JNK activation) induce significant amounts of inflammatory mediators from various cell types, they need to be tightly controlled. We have recently cloned a novel MAP kinase phosphatase, MKP-M, and found that it is specifically essential in the downregulation of JNK activity induced by LPS. LPS has been identified as an important pathogenic factor of periodontitis. We found that osteoblasts express both TLR2 and TLR4 mRNAs and directly respond to LPS by increasing RANKL protein expression. Mice with disrupted RANKL gene completely lack osteoclasts and exhibit severe osteopetrosis and a defect in tooth eruption, suggesting that RANKL is essential for osteoclastgenesis. Thus, LPS may promote periodontitis by directly inducing RANKL expression via TLRs in osteoblasts.
- 鹿児島大学の論文
- 2004-03-25
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- TLRシグナルと歯周病