Synergism between lipopolysaccharide and interferon gamma in the regulation of lipoprotein lipase in macrophages

The regulation of macrophage lipoprotein lipase (LPL) by cytokines is poten tially of crucial importance in the pathogenesis of atherosclerosis and in septic shock, The effect of combinations of lipopolysaccharide (LPS) and cy tokines on the expression of LPL in macrophages was studied using the murin e J774.2 cell line, The suppression of heparin-releasable LPL activity prod uced by combinations of LPS and interleukin 1 (IL-1), IL-11 or tumour necro sis factor a (TNF-alpha) was substantially less than that expected from the simple additive action of the corresponding two effecters, By contrast, co -exposure of the cells to LPS and interferon gamma (IFN-gamma) resulted in a more than additive, synergistic, suppression of LPL activity which was, a dditionally, also observed when the rat alveolar macrophage NR8383 cell lin e was studied, This synergistic action was also observed when J774.2 macrop hages were exposed initially to IFN-gamma (priming), washed and then treate d with LPS,A comparison of the LPL activity and mRNA levels produced by the synergistic action of LPS and IFN-gamma and the priming action of IFN-gamm a indicated that a combination of mRNA metabolism (transcription or RNA sta bility), translation and post-translational mechanisms were responsible for the observed changes in LPL activity, These data, therefore, suggest that combinations of LPS and cytokines may be more important than the presence o r absence of any given single effector in the modulation of LPL function du ring infection. (C) 1999 Academic Press.