Hydroxyethyl starch 130/0.4 exerts its anti-inflammatory effect in endotoxemic rats by inhibiting the TLR4/NF-kappaB signaling pathway.
Previous studies demonstrated that hydroxyethyl starch (HES) down-regulates the inflammatory response, but the mechanism is controversial. The present study measured the effects of HES130/0.4 on plasma proinflammatory cytokines levels and the Toll-like receptor-4 (TLR4)/nuclear factor-kappa B (NF-kappaB) signaling pathway in lipopolysaccharide (LPS)-treated rats. Endotoxemia was induced in rats by injection of LPS (5 mg/kg, via tail vein) and the rats were infused with different doses of HES130/0.4 (7.5, 15, or 30 ml/kg, via jugular vein). At 2 hr after the injection of LPS, plasma and peripheral monocytes were collected to determine tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta concentrations (enzyme-linked immunosorbent assay), NF-kappaB activities (electrophoretic mobility shift assay), TLR4 mRNA expression (reverse transcription-polymerase chain reaction), and TLR4 protein levels (Western blotting). The infusion of HES130/0.4 in endotoxemic rats, especially 15 ml/kg, significantly reduced the release of plasma TNF-alpha and IL-1beta, which was consistent with the observed inhibitory effects of HES130/0.4 on NF-kappaB activation, TLR4 mRNA expression, and TLR4 protein level in monocytes. Thus, HES130/0.4 evidently exerts its anti-inflammatory effect in endotoxemic rats by inhibiting the TLR4/NF-kappaB signaling pathway, which suggests that HES130/0.4 may useful for treating early Gram-negative sepsis.
Xie
Junran
J
Department of Anesthesiology, Sir Run Run Shaw Hospital, Hangzhou 310016, P. R. China.
Lv
Ran
R
Yu
Lina
L
Huang
Weidong
W
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D019446:Endotoxemia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010952:Plasma Substitutes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D006895:Hydroxyethyl Starch Derivatives; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010952:Plasma Substitutes; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha