TLR-independent induction of human monocyte IL-1 by phosphoglycolipids from thermophilic bacteria

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• 作者：Feng-Ling Yang ; Kuo-Feng Hua ; Yu-Liang Yang ; Wei Zou ; Yen-Po Chen ; Shu-Mei Liang ; Hsien-Yeh Hsu and Shih-Hsiung Wu
• 关键词：Phosphoglycolipids ; Thermophilic bacteria ; Immunomodulators
• 刊名：Glycoconjugate Journal
• 出版年：2008
• 出版时间：July, 2008
• 年：2008
• 卷：25
• 期：5
• 页码：427-439
• 全文大小：423.6 KB

文摘

The structures of phosphoglycolipids PGL1 and PGL2 from the thermophilic bacteria Meiothermus taiwanensis, Meiothermus ruber, Thermus thermophilus, and Thermus oshimai are determined recently (Yang et al. in J Lipid Res. 47:1823–1932, 2006). These bacteria belong to Gram-negative bacteria that do not contain lipopolysaccharide, but high amounts of phosphoglycolipids and glycoglycerolipids. Here we show that PGL1/PGL2 mixture (PGL1: PGL2 = 10:1 ~ 10:2) from M. taiwanensis and T. oshimai, but not T. thermophilus and M. ruber, up-regulate interleukin-1β (IL-1β) production in human THP-1 monocytes and blood-isolated primary monocytes. PGL2 was purified after phospholipase A2 hydrolysis of PGL1 in the PGL1/PGL2 mixture followed by column chromatography. PGL2 did not induce proIL-1 production, even, partially (35–40 % ) inhibited PGL1-mediated proIL-1 production, showing that PGL1 is the main inducer of proIL-1 production in PGL1/PGL2 mixture. The production of proIL-1 stimulated by phosphoglycolipids was strongly inhibited by specific PKC-α, MEK1/2, and JNK inhibitors, but not by p38-specific inhibitor. The intracellular calcium influx was involved in phosphoglycolipids-mediated proIL-1 production. Using blocking antibody and Toll-like receptor (TLR)-linked NF-κB luciferase assays, we found that the cellular receptor(s) for phosphoglycolipids on proIL-1 production was TLR-independent. Further, phosphoglycolipids isolated from T. thermophilus and M. ruber did not induce proIL-1 production, even though T. thermophilus possess more PGL1 than PGL2 (6:4). Specially, the fatty acid composition of phosphoglycolipids from both T. thermophilus and M. ruber consists of a low percentage of C15 (<10 % ) and a high percentage of C17 (>75 % ). It suggests, the C15 percentage of PGL may play a critical role in PGL-mediated proIL-1 induction.