A dipalmitoylated lipoprotein from Mycoplasma pneumoniae activates NF-kappa B through TLR1, TLR2, and TLR6.
The pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributed to excessive immune responses. Recently, lipoproteins from mycoplasmas have been reported to induce NF-kappaB activation. In this study, we examined the ability of lipoproteins from M. pneumoniae to activate NF-kappaB, and the active component responsible for the NF-kappaB activation was identified. Lipid-associated membrane proteins from M. pneumoniae were found to induce NF-kappaB through TLR 2 in a human monocytic cell line, THP-1. The active component of the Lipid-associated membrane proteins was a subunit b of F0F1-type ATPase (F0F1-ATPase). The F0F1-ATPase is assumed to contain two palmitic acids. The activation of NF-kappaB by the F0F1-ATPase was inhibited by a dominant negative construct of TLR1 and TLR6. These results indicate that the activation of NF-kappaB by F0F1-ATPase is dependent on TLR1, TLR2, and TLR6. The activity of the F0F1-ATPase was decreased with pretreatment of lipoprotein lipase but not protease, indicating that the lipid moiety of the F0F1-ATPase was important for the NF-kappaB activation. Thus, a dipalmitoylated lipoprotein from M. pneumoniae was found to activate NF-kappaB through TLR1, TLR2, and TLR6.
Shimizu
Takashi
T
Department of Bacteriology, Kurume University School of Medicine, Kurume, Japan.
Kida
Yutaka
Y
Kuwano
Koichi
K
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D025243:Bacterial Proton-Translocating ATPases / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D008074:Lipoproteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009177:Mycoplasma pneumoniae / Q000276:immunology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism*; D011019:Pneumonia, Mycoplasma / Q000276:immunology*
D000911:Antibodies, Monoclonal; D008074:Lipoproteins; D016328:NF-kappa B; D019308:Palmitic Acid; D025243:Bacterial Proton-Translocating ATPases