LPS suppresses expression of asialoglycoprotein-binding protein through TLR4 in thioglycolate-elicited peritoneal macrophages
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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.
KeywordsMacrophage asialoglycoprotein-binding protein C-type lectin LPS TLR4 NF-κB
macrophage asialoglycoprotein-binding protein
macrophage C-type galactose/N-acetylgalactosamine-specific lectin
toll-like receptor 4
mitogen-activated protein kinase
extracellular signal-regulated protein kinase
c-Jun amino-terminal kinase
nuclear factor kappa B
inhibitor of NF-κB
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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