Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced acute lung injury by inhibition of CD14 and TLR4 expression

Abstract

We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1β levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.

Effects of propofol pretreatment on lung morphology and heme oxygenase-1 expression in oleic acid-induced acute lung injury in rats

“…The expression of HO-1 was significantly lower in group OA+IX than in group OA (P<0.01), which showed that HO-1 expression was inhibited by zinc porphyrin IX. Consequently, the high expression of HO-1 in group OA+PR was related to propofol, which is consistent with related reports [25][26][27][28][29] . This effect was confirmed by lung histomorphology analysis by light microscopy and AEC-II ultrastructure analysis by electron microscopy.…”

Effects of ketamine, propofol, and ketofol on proinflammatory cytokines and markers of oxidative stress in a rat model of endotoxemia-induced acute lung injury.

“…Propofol has shown anti-inflammatory effect by decreasing cytokine levels in bronchoalveolar lavage fluid (BALF) of LPS-induced endotoxemic rats. Furthermore, LPS injection increased the mRNA and protein levels of inflammation releated genes, TRL4 and CD14 in lung parenchyma and propofol treatment decreased both mRNA and protein levels of CD14 and TRL4 (Ma et al, 2013). The present findings showed that propofol treatment reduced the level of circulating cytokines, but had no effect on NF-κB mRNA level in lung tissue.…”

Propofol attenuated TNF-α-modulated occludin expression by inhibiting Hif-1α/ VEGF/ VEGFR-2/ ERK signaling pathway in hCMEC/D3 cells

“…It was revealed that propofol reversed TNF-αinduced human vascular endothelial cells apoptosis [28]. It has also been reported that propofol exerted antiinflammatory effects in rats [29]. In this study, propofol inhibited lipopolysaccharide-induced acute lung injury by inhibition of cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression [29].…”