Toll-like receptor 3 ligand-induced antiviral response in mouse osteoblastic cells.
Double-stranded RNA (dsRNA) and its mimic, polyinosinic acid:polycytidylic acid [poly(I):poly(C)], are recognized by toll-like receptor 3 (TLR3) that induces the production of IFN-beta in many cell types. In the present study, we investigated the effects of poly(I):poly(C) on mouse osteoblastic MC3T3-E1 (E1) cells. Poly(I):poly(C) markedly increased IFN-beta mRNA level in a dose-dependent manner. The increase in the IFN-beta mRNA level was apparent as early as 1 h after adding poly(I):poly(C) to the culture and peaked at 12 h. Stimulation with poly(I):poly(C) enhanced the expression of CXCL10 mRNA and TLR3 in E1 cells. Moreover, poly(I):poly(C) induced tyrosine phosphorylation of the transcription factor STAT1 in E1 cells. An anti-IFN-beta neutralizing antibody partially inhibited poly(I):poly(C)-induced CXCL10 mRNA, TLR3 mRNA and STAT1 phosphorylation. These results indicate that osteoblasts secrete IFN-beta in response to viral infection and that endogenous IFN-beta induces both CXCL10 and TLR3 production via an IFN-alpha/beta receptor-STAT1 pathway. It is suggested that osteoblasts are involved in host defense as well as bone metabolism.
Nakamura
Kimiya
K
Department of Preventive Dentistry, Division of Oral Health Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan.
Deyama
Yoshiaki
Y
Yoshimura
Yoshitaka
Y
Suzuki
Kuniaki
K
Morita
Manabu
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000998:Antiviral Agents / Q000276:immunology*; D019898:Autocrine Communication / Q000187:drug effects; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D009500:Neutralization Tests; D010006:Osteoblasts / Q000187:drug effects / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*
D000906:Antibodies; D000998:Antiviral Agents; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D008024:Ligands; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D011070:Poly I-C