AIM: To investigate whether ketamine suppresses lipopolysaccharide (LPS)-induced increase in Toll-like receptor 4 (TLR4) expression and nuclear factor-kappa B (NF-kappaB) activity in the intestines of rats. METHODS: Six groups of rats received one of the following: normal saline control, LPS (5 mg/kg) plus saline, LPS (5 mg/kg) plus ketamine (0.5 mg/kg), LPS (5 mg/kg) plus ketamine (2.5 mg/kg), LPS (5 mg/kg) plus ketamine (10 mg/kg), or ketamine (10 mg/kg) alone. Intestinal TLR4 mRNA expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and NF-kappaB activity was tested by electrophoretic mobility shift assay (EMSA) 1, 3, or 5 hours after the LPS injection. RESULTS: Lipopolysaccharide increased TLR4 expression and NF-kappaB activity in the intestines of rats. Ketamine at the dosage of 0.5, 2.5, and 10 mg/kg suppressed the LPS-induced increase in TLR4 expression and NF-kappaB activity. Ketamine alone had no effect. CONCLUSION: The study demonstrated that ketamine inhibits NF-kappaB activation in the intestines of LPS-treated rats, possibly by suppressing TLR4 expression.
AIM: To investigate whether ketamine suppresses lipopolysaccharide (LPS)-induced increase in Toll-like receptor 4 (TLR4) expression and nuclear factor-kappa B (NF-kappaB) activity in the intestines of rats. METHODS: Six groups of rats received one of the following: normal saline control, LPS (5 mg/kg) plus saline, LPS (5 mg/kg) plus ketamine (0.5 mg/kg), LPS (5 mg/kg) plus ketamine (2.5 mg/kg), LPS (5 mg/kg) plus ketamine (10 mg/kg), or ketamine (10 mg/kg) alone. Intestinal TLR4 mRNA expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and NF-kappaB activity was tested by electrophoretic mobility shift assay (EMSA) 1, 3, or 5 hours after the LPS injection. RESULTS:Lipopolysaccharide increased TLR4 expression and NF-kappaB activity in the intestines of rats. Ketamine at the dosage of 0.5, 2.5, and 10 mg/kg suppressed the LPS-induced increase in TLR4 expression and NF-kappaB activity. Ketamine alone had no effect. CONCLUSION: The study demonstrated that ketamine inhibits NF-kappaB activation in the intestines of LPS-treated rats, possibly by suppressing TLR4 expression.
Authors: A Poltorak; X He; I Smirnova; M Y Liu; C Van Huffel; X Du; D Birdwell; E Alejos; M Silva; C Galanos; M Freudenberg; P Ricciardi-Castagnoli; B Layton; B Beutler Journal: Science Date: 1998-12-11 Impact factor: 47.728