Lipopolysaccharide signaling induces serum amyloid A (SAA) synthesis in human hepatocytes in vitro.
To investigate the role of lipopolysaccharide (LPS) in hepatocyte activation, we examined the expression of Toll-like receptor 4 (TLR4), the putative receptor for LPS in human hepatocytes. TLR4 mRNA and protein expression was confirmed in human hepatocytes. Stimulation of human hepatocytes with LPS results in rapid degradation of IkappaB-alpha and mitogen activated protein kinase activation. Human hepatocytes stimulated by LPS produced serum amyloid A protein. Our data suggest that human hepatocytes utilize components of TLR4 signal transduction pathways in response to LPS and these direct LPS-mediated effects on hepatocytes may contribute to liver inflammation and injury.
Migita
Kiyoshi
K
Clinical Research Center, National Nagasaki Medical Center, Kubara 2-1001-1, Omura 856-8562, Japan. migita@nmc.hosp.go.jp
Abiru
Seigo
S
Nakamura
Minoru
M
Komori
Atsumasa
A
Yoshida
Yuki
Y
Yokoyama
Terufumi
T
Daikoku
Manabu
M
Ueki
Toshihito
T
Takii
Yasushi
Y
Yano
Koji
K
Yastuhashi
Hiroshi
H
Eguchi
Katsumi
K
Ishibashi
Hiromi
H
D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D000685:Serum Amyloid A Protein / Q000096:biosynthesis*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014158:Transcription, Genetic / Q000187:drug effects
D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000685:Serum Amyloid A Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors