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

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Abstract

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.

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Acknowledgments

This work was supported by National Science Council, Taiwan, (NSC 92-2321-B-001-019 and 94-2311-B-001-045 to S-H Wu; NSC 93-2314-B-010-003 and 94-2120-M-010-002 to H-Y Hsu); National Health Research Institutes, Taiwan (NHRI-EX93-9211SI and support for the cost of reprints to H-Y Hsu); the Ministry of Education, Taiwan, on Program for Promoting Academic Excellence of Universities (A-91-B-FA09-2-4 to H-Y Hsu); a grant from Ministry of Education, Aim for the Top University Plan (95A-C-D01-PPG-10 to H-Y Hsu); Academia Sinica (Thematic project to H-Y Hsu).

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  1. Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan

    Feng-Ling Yang, Yu-Liang Yang & Shih-Hsiung Wu

  2. Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, 112, Taiwan

    Kuo-Feng Hua & Hsien-Yeh Hsu

  3. Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, K1A 0R6, Canada

    Wei Zou

  4. Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 115, Taiwan

    Yen-Po Chen & Shu-Mei Liang

  5. Department of Education and Research, Taipei City Hospital, Taipei, 112, Taiwan

    Hsien-Yeh Hsu

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Feng-Ling Yang and Kuo-Feng Hua equally contributed.

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Yang, FL., Hua, KF., Yang, YL. et al. TLR-independent induction of human monocyte IL-1 by phosphoglycolipids from thermophilic bacteria. Glycoconj J 25, 427–439 (2008). https://doi.org/10.1007/s10719-007-9088-2

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