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LPS suppresses expression of asialoglycoprotein-binding protein through TLR4 in thioglycolate-elicited peritoneal macrophages

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Abstract

Macrophages are known to express various types of endocytosis receptors that mediate the removal of foreign pathogens. Macrophage asialoglycoprotein-binding protein (M-ASGP-BP) is a Gal/GalNAc-specific lectin, which functions as an endocytosis receptor. We found here that LPS is able to down-regulate the mRNA expression of M-ASGP-BP in a time-dependent manner using thioglycolate-elicited rat and mouse peritoneal macrophages. However, LPS does not modulate the mRNA expression of M-ASGP-BP from macrophages of C3H/HeN mice, which have a point mutation of TLR4, the primary LPS receptor. Furthermore, an inhibitor of NF-κB was observed to efficiently block the suppressive effect of LPS on M-ASGP-BP as well as to inhibit the phosphorylated IκB. These results demonstrate that the mRNA expression of M-ASGP-BP is down-regulated by the LPS-mediated TLR4 pathway involving NF-κB activation, suggesting that engagement of M-ASGP-BP by LPS may yield a negative signal that interferes with the LPS-induced positive signals mediated by proinflammatory cytokines.

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Abbreviations

M-ASGP-BP:

macrophage asialoglycoprotein-binding protein

MGL:

macrophage C-type galactose/N-acetylgalactosamine-specific lectin

Mϕ:

macrophage

LPS:

lipopolysaccharide

TLR4:

toll-like receptor 4

MAPK:

mitogen-activated protein kinase

ERK:

extracellular signal-regulated protein kinase

JNK:

c-Jun amino-terminal kinase

NF-κB:

nuclear factor kappa B

IκB:

inhibitor of NF-κB

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Acknowledgments

The authors would like to thank Ms. Tomoko Tominaga for the secretarial assistance.

This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas, A-14082203, to T. Kawasaki, and for Scientific Research, C-18590471, to B.Y. Ma from the Japan Society for the Promotion of Science, Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to Bruce Yong Ma or Toshisuke Kawasaki.

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Ma, B.Y., Kaihama, M., Nonaka, M. et al. LPS suppresses expression of asialoglycoprotein-binding protein through TLR4 in thioglycolate-elicited peritoneal macrophages. Glycoconj J 24, 243–249 (2007). https://doi.org/10.1007/s10719-007-9031-6

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