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Endotoxin suppresses mouse hepatic low‐density lipoprotein–receptor expression via a pathway independent of the toll‐like receptor 4
Author(s) -
Liao Wei,
Rudling Mats,
Angelin Bo
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510300524
Subject(s) - endocrinology , medicine , ldl receptor , receptor , lipopolysaccharide , hyperlipidemia , toll like receptor , tlr4 , lipoprotein , very low density lipoprotein , biology , chemistry , cholesterol , innate immune system , diabetes mellitus
Endotoxin provokes an inflammatory state in the infected host. C3H/HeJ mice are tolerant to endotoxin because of an Lps gene mutation. Recent studies have identified that this gene encodes the Toll‐like receptor 4. Endotoxin also induces hyperlipidemia and suppresses hepatic low‐density lipoprotein (LDL)–receptor expression. In the current study, we investigated whether a defective Lps gene would impair the hepatic LDL‐receptor response to endotoxin in C3H/HeJ mice. Eighteen hours after an intraperitoneal injection of endotoxin, the hepatic LDL‐receptor expression and the plasma lipoprotein pattern were analyzed. Endotoxin increased plasma triglyceride and apoE in very low‐density lipoproteins (VLDL) and intermediate‐density lipoproteins, and decreased apoAI in high‐density lipoproteins (HDL) in the endotoxin‐sensitive mice (C3H/HeN), but not in the endotoxin‐resistant mice (C3H/HeJ). These data indicate that a defective Lps gene impairs the endotoxin signaling to alter these lipoproteins. However, the hepatic LDL‐receptor response to endotoxin in the endotoxin‐resistant mice was similar to that in the endotoxin‐sensitive mice. Thus, at a dose of 5 μg/mouse, endotoxin reduced hepatic LDL‐receptor expression by 35% in C3H/HeN mice and by 52% in C3H/HeJ mice. At a dose of 50 μg/mouse, endotoxin reduced hepatic LDL‐receptor expression by 61% in C3H/HeN mice and by 63% in C3H/HeJ mice. It is concluded that endotoxin suppresses hepatic LDL‐receptor expression in vivo via a pathway independent of the Toll‐like receptor 4.