LPS suppresses expression of asialoglycoprotein-binding protein through TLR4 in thioglycolate-elicited peritoneal macrophages.
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-kappaB was observed to efficiently block the suppressive effect of LPS on M-ASGP-BP as well as to inhibit the phosphorylated IkappaB. These results demonstrate that the mRNA expression of M-ASGP-BP is down-regulated by the LPS-mediated TLR4 pathway involving NF-kappaB 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.
Ma
Bruce Yong
BY
Research Center for Glycobiotechnology, Ritsumeikan University, Shiga, 525-8577, Japan. byma@fc.ritsumei.ac.jp
Kaihama
Mio
M
Nonaka
Motohiro
M
Oka
Shogo
S
Kawasaki
Nobuko
N
Kawasaki
Toshisuke
T
D000818:Animals; D001212:Asialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013864:Thioglycolates / Q000494:pharmacology; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D001212:Asialoglycoproteins; C064720:Clec10a protein, mouse; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D013864:Thioglycolates; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4