Effects of ketamine on pulmonary TLR4 expression and NF-kappa-B activation during endotoxemia in rats.
The aim of the study was to investigate the effects of ketamine on pulmonary Toll-like receptor 4 (TLR4) expression and nuclear factor kappa-B (NF-kappa-B) activity in rats with endotoxemia. Rats were treated with lipopolysaccharide (LPS, 5 mg/kg) to induce endotoxemia, followed immediately by ketamine (0.5, 5 and 10 mg/kg) or 0.9% NaCl (5 ml/kg). At 1, 3 and 5 h posttreatment, TLR4 mRNA expression and NF-kappa-B activity of the rat lungs were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA), respectively. LPS increased TLR4 expression and NF-kappa-B activity in the rat lungs. Ketamine at the dose levels of 5 and 10 mg/kg suppressed the LPS-induced elevation of TLR4 expression and NF-kappa-B activity. Ketamine alone had no effect on either one of them. The present study revealed that ketamine could inhibit pulmonary NF-kappa-B activity during endotoxemia in rats, and this antiinflammatory effect possibly acts through suppressing TLR4 expression.
Yu
M
M
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Shao
D
D
Feng
X
X
Duan
M
M
Xu
J
J
D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism*; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
D000778:Anesthetics, Dissociative; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D007649:Ketamine