Lipopolysaccharide Is a Cofactor for Malondialdehyde‐Acetaldehyde Adduct–Mediated Cytokine/Chemokine Release by Rat Sinusoidal Liver Endothelial and Kupffer Cells

Abstract

These studies strongly suggest that the sensitization of SECs and KCs by LPS plays a significant role in the development and/or progression of alcoholic liver disease, and the subsequent activation by MAA-modified proteins may be a mechanism by which proinflammatory processes are initiated.

Scavenger Receptors on Sinusoidal Liver Endothelial Cells Are Involved in the Uptake of Aldehyde-Modified Proteins

“…Sinusoidal liver endothelial cells were prepared by perfusion and differential centrifugation methods as described previously (Braet et al, 1994;Duryee et al, 2004). Cell number and viability was determined by trypan blue exclusion and counting on a hemocytometer.…”

TLR4, Ethanol, and Lipid Rafts: A New Mechanism of Ethanol Action with Implications for other Receptor-Mediated Effects

“…This is consistent with the idea that adaptation is induced by chronic EtOH exposure. It should also be noted that effects of chronic EtOH exposure on the immune system can be relatively persistent, and mechanisms such as increased production of reactive oxygen species and cellular damage caused by the reactive EtOH metabolite acetaldehyde have been implicated in chronic effects of EtOH on the immune system (32,33). In addition, the effects of acute EtOH exposure on lipid rafts discussed later in this review are relatively short-lived.…”

Rat sinusoidal liver endothelial cells (SECs) produce pro-fibrotic factors in response to adducts formed from the metabolites of ethanol

“…Previous studies in our laboratory have shown the induction by MAA-adducts of pro-inflammatory cytokines/chemokines and adhesion molecules [13,15]. An increase in fibronectin secretion by SECs of the liver in response to MAA-adduct stimulation may be one method by which chronic alcohol consumption induces fibrosis leading to cirrhosis.…”

“…Briefly, following isolation cells were counted on a hemocytometer and the viability was determined by trypan blue exclusion, and found to be greater than 85% viable. SEC purity was assessed by staining with antibodies specific for the various cell types of the liver using a Fluorescent Activated Cell Scanner (FACSCalibur, San Jose, CA) as previously reported [13]. SECs were determined to be >90% pure.…”

“…The ability of malondialdehyde and acetaldehyde to react with proteins to form the stable hybrid adduct (MAA) [11] has profound implications in the onset of alcoholic liver disease [12]. The MAA-adduct has been shown to cause the release of cytokines/chemokines by SECs, KCs, and stellate cells [13][14][15]. It is known that cytokines, growth factors, hormones, and enzymes are present in their inactive form and upon activation, can alter the ECM and initiate the fibrogenic process [16].…”