ABSTRACT
Synthesis and secretion of IL-1beta and IL-6 were compared in LPS-stimulated rat peritoneal macrophages, and the effect of glutamine studied. LPS induced a parallel increase in mRNA and synthesis of IL-1beta and IL-6. IL-1beta accumulated mainly in the cytosol and IL-6 in the culture medium. Glutamine addition increased the synthesis of both cytokines, but the overall production (intra-+extracellular) of IL-1beta increased two-fold, although that of IL-6 increased only 1.3-fold. The influence of glutamine is discussed.
Subject(s)
Glutamine/pharmacology , Interleukin-1/biosynthesis , Interleukin-6/biosynthesis , Macrophages, Peritoneal/drug effects , Animals , In Vitro Techniques , Lipopolysaccharides/pharmacology , Macrophages, Peritoneal/metabolism , Male , Rats , Rats, WistarABSTRACT
Glutamine is able to regulate the expression of various genes in rat hepatocytes. This includes genes coding for proteins involved in glutamine utilization, such as argininosuccinate synthetase (ureagenesis) or phosphoenolpyruvate carboxykinase (gluconeogenesis). Moreover, glutamine is also able to stimulate the expression of genes involved in the acute-phase response, such as the alpha 2-macroglobulin gene. The effect of glutamine on the regulation of gene expression may be explained, at least in part, by the cell swelling due to its sodium-dependent transport. The physiological significance of the effect of glutamine is discussed.
Subject(s)
Gene Expression Regulation , Glutamine/physiology , Liver/metabolism , Aminoisobutyric Acids/metabolism , Animals , Argininosuccinate Synthase/genetics , Argininosuccinate Synthase/metabolism , Cell Size/physiology , Dose-Response Relationship, Drug , Interleukin-6/metabolism , Models, Biological , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Phosphoenolpyruvate Carboxykinase (ATP)/metabolism , Rats , Time Factors , alpha-Macroglobulins/genetics , alpha-Macroglobulins/metabolismABSTRACT
The effect of glutamine on the production of interleukin-6 (IL-6) was studied in rat peritoneal macrophages in culture. A maximal production of IL-6 was measured at 4 h in lipopolysaccharide (LPS)-stimulated macrophages, and addition of glutamine (5 mM) anticipated this increase by 1 h without any increase in the IL-6 mRNA level. The effect of glutamine required the presence of LPS. Thus, glutamine accelerates IL-6 production from the pre-existing mRNA. The effect of glutamine was not mediated by cell swelling since culture of macrophages in hypoosmotic condition decreased the production of IL-6 in the culture medium with a corresponding decrease in the IL-6 mRNA level.
