The diacylated lipopeptide FSL-1 induces TLR2-mediated Th2 responses.
The diacylated lipopeptide FSL-1 enhanced the generation of IgG antibodies in TLR2(+/+) mice, but not in TLR2(-/-) mice, when administered together with hen egg lysozyme as an antigen. Escherichia coli lipopolysaccharide enhanced the generation of antigen-specific antibodies in both TLR2(-/-) and TLR2(+/+) mice. In TLR2(+/+) mice, the level of enhancement due to FSL-1 was similar to that caused by lipopolysaccharide. Analysis of the IgG antibodies subclass demonstrated that the level of Th2-type IgG1 antibodies was higher than that of Th1-type IgG2a antibodies. Both FSL-1 and lipopolysaccharide induced production of IL-10 and IL-6 by splenocytes from TLR2(+/+) mice. Lipopolysaccharide also induced production of these cytokines by splenocytes from TLR2(-/-) mice, but FSL-1 did not. Neither FSL-1 nor lipopolysaccharide induced IL-12p70 production by splenocytes from either type of mice. FSL-1 upregulated B7.2 expression in B220(+) cells from TLR2(+/+) mice but not those from TLR2(-/-) mice, whereas lipopolysaccharide upregulated B7.2 expression in B220(+) cells from both types of mice. FSL-1 and, to a lesser extent, lipopolysaccharide activated mitogen-activated protein kinases in splenocytes. FSL-1 and, to a lesser extent, lipopolysaccharide induced the expression of c-Fos, which is known to be involved in Th2-type responses, in splenocytes. Thus, this study demonstrated that FSL-1 possessed TLR2-mediated Th2-type responses in vivo.
Kiura
Kazuto
K
Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan.
Kataoka
Hideo
H
Yasuda
Motoaki
M
Inoue
Nobuo
N
Shibata
Ken-ichiro
K
D000215:Acylation; D000818:Animals; D004075:Diglycerides / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D004075:Diglycerides; C460864:FSL-1 lipoprotein, synthetic; D009842:Oligopeptides; D051195:Toll-Like Receptor 2