title: Defect of toll-like receptor 9-mediated activation in NC/Nga mouse macrophages.
abstract: Toll-like receptors (TLRs) control activation of adaptive immune responses by antigen-presenting cells (APCs). In this study, we examined TLR9-mediated activation in NC/Nga mice, an animal model for human atopic dermatitis. NC/Nga mouse macrophages produced significantly less TNF-alpha than did BALB/c mouse macrophages in response to CpG oligonucleotide (ODN). In addition to defective TLR9-mediated TNF-alpha production, phosphorylation of ERK1,2 and p38 was rapidly diminished after 60 min of CpG ODN stimulation, whereas phosphorylation of these molecules was sustained until 60 min in BALB/c mice. Furthermore, phosphorylation of c-Jun N-terminal kinase (JNK) was not observed in NC/Nga mouse macrophages. In contrast, B cells and dendritic cells (DCs) from NC/Nga mice showed normal responses to CpG ODN stimulation. The expression level of TLR9 in NC/Nga mouse macrophages was significantly lower than that in BALB/c mouse macrophages, whereas levels of TLR9 expression in B cells and DCs in NC/Nga mice were the same as those in BALB/c mice. These results suggest that defective TLR9-mediated activation in NC/Nga mouse macrophages contributes to the reduction of TLR9 expression levels.
authors.affiliation: Department of International Nutrition, Institution of Health Bioscience, The University of Tokushima Graduate School, Japan. tohrus@nutr.med.tokushima-u.ac.jp
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakai
authors.forename: Mari
authors.initials: M
authors.lastname: Kogiso
authors.forename: Kaori
authors.initials: K
authors.lastname: Mitsuya
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Komatsu
authors.forename: Sigeru
authors.initials: S
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9