Synergy of TRIF-dependent TLR3 and MyD88-dependent TLR7 in up-regulating expression of mouse FPR2, a promiscuous G-protein-coupled receptor, in microglial cells.
Human G-protein-coupled formyl peptide receptor-like 1 and its mouse homologue formyl peptide receptor 2 mediate the chemotactic activity of a variety of pathogen and host-derived peptides, including amyloid beta(42), a key causative factor in Alzheimer's disease (AD).Here, we found that polyinosine-polycytidylic acid (Poly(I:C)), which is a specific TLR3 ligand, and Imiquimod (R837), which is a specific TLR7 ligand, when used alone, each increased MAPK-dependent functional mFPR2 expression in microglial cells, and the combination of Poly(I:C) and R837 exhibited additive effect by enhancing the level of IkappaB-alpha phosphorylation. Our results indicated that RNA virus infection may actively participate in the pathogenic processes of brain inflammation and neurodegenerative diseases by TLR3- and TLR7-mediated TRIF-dependent and MyD88-dependent signaling pathways.
Chen
Keqiang
K
School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai, PR China.
Huang
Jian
J
Liu
Ying
Y
Gong
Wanghua
W
Cui
Youhong
Y
Wang
Ji Ming
JM
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004357:Drug Synergism; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D005911:Gliosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D020672:I-kappa B Proteins / Q000378:metabolism; D000077271:Imiquimod; D020935:MAP Kinase Signaling System / Q000502:physiology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation / Q000187:drug effects; D011070:Poly I-C / Q000494:pharmacology; D012327:RNA Virus Infections / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000187:drug effects / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D033942:Adaptor Proteins, Vesicular Transport; D000634:Aminoquinolines; D020672:I-kappa B Proteins; D000077271:Imiquimod; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D000072000:NF-KappaB Inhibitor alpha; D011070:Poly I-C; D044042:Receptors, Formyl Peptide; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; C507780:Myd88 protein, mouse; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C476286:Ticam1 protein, mouse; C519703:TLR3 protein, mouse; C477038:Tlr7 protein, mouse; C481578:formyl peptide receptor 2, mouse