Chylomicron-bound LPS selectively inhibits the hepatocellular response to proinflammatory cytokines.

Abstract

BACKGROUND/AIMS: Pretreatment of rodent hepatocytes with chylomicron-bound lipopolysaccharide (CM-LPS) renders these cells unresponsive to subsequent stimulation by proinflammatory cytokines. We sought to test the selectivity of this response. METHODS: Cellular responses to hypoxia, oxidative stress, apoptosis, and heat-shock response, and thermotolerance induced in CM-LPS pretreated hepatocytes were compared with responses in non-pretreated cells. RESULTS: CM-LPS inhibited the hepatocellular response to proinflammatory cytokines without affecting the response to the other cellular stressors. It did not affect the response to oxidative stress, as measured by mitochondrial activity after hydrogen peroxide was added, or protein induction before or after stimulation with cobalt chloride. Also, induction of heat shock proteins did not differ between the CM-LPS pretreated cells and non-pretreated cells. CM-LPS did not interfere with the adoption of the thermotolerant phenotype, as shown by similar mitochondrial activity between pretreated and non-pretreated cells. Although stimulation with tumor necrosis factor-alpha and actinomycin D increased activity of the apoptotic enzymes, there were no differences between cells pretreated with CM-LPS and non-pretreated hepatocytes. CONCLUSION: When the response to proinflammatory cytokines is inhibited, hepatocellular responses to hypoxia, oxidative stress, heat shock, and apoptosis remain intact after pretreatment with CM-LPS. CM-LPS may have a specific anti-inflammatory effect on hepatocytes.