Permalink : http://hdl.handle.net/2115/45804

KEYWORDS : Toll-like receptor 2;Toll-like receptor 4;Aging

Splenocytes prepared from 8-week old and 20-month old C57BL/6 mice were stimulated with various concentrations of the TLR2 ligand FSL-1 or the TLR4 ligand E. coli LPS and the growth of the splenocytes was measured. Both FSL-1 and E. coli LPS stimulated the growth of the cells from the young mice more strongly than that from the aged mice in a dose-dependent manner. The splenocytes from the young and aged mice expressed both TLR2 and TLR4 on the cell surface and the expression levels of both TLRs were higher in the young mice than in the old mice. The expression and functions of TLR2 and TLR4 were then examined with nine each of 60-week and 8-week old mice. The expression levels of TLR4 were significantly higher in the young mice than in the aged mice, whereas the expression level of TLR2 was significantly lower in the young mice than in the aged mice. However, the amounts of TNF-α and IL-6 produced by splenocytes from the young mice were significantly larger than those from the aged mice, suggesting that the function of TLRs is impaired in the aged mice. The expression and functions of TLR2 and TLR4 in human PBMC were also examined. The expression levels of both TLR2 and TLR4 in the young individuals were slightly but not statistically significantly higher than those in the aged individuals. FSL-1 but not the LPS stimulation induced significantly larger amounts of IL-6 in young human adults when compared with aged adults. In addition, both FSL-1 and LPS stimulation induced significantly larger amounts of TNF-α in young volunteers than in those from the aged ones. Thus, the present study suggests that the functions of TLR2 and TLR4 become defective with aging in humans and mice.