Synergism between lipopolysaccharide and interferon gamma in the regulation of lipoprotein lipase in macrophages.
The regulation of macrophage lipoprotein lipase (LPL) by cytokines is potentially of crucial importance in the pathogenesis of atherosclerosis and in septic shock. The effect of combinations of lipopolysaccharide (LPS) and cytokines on the expression of LPL in macrophages was studied using the murine J774.2 cell line. The suppression of heparin-releasable LPL activity produced by combinations of LPS and interleukin 1 (IL-1), IL-11 or tumour necrosis factor alpha(TNF-alpha) was substantially less than that expected from the simple additive action of the corresponding two effectors. 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, additionally, also observed when the rat alveolar macrophage NR8383 cell line was studied. This synergistic action was also observed when J774.2 macrophages were exposed initially to IFN-gamma (priming), washed and then treated 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-gamma indicated that a combination of mRNA metabolism (transcription or RNA stability), 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 or absence of any given single effector in the modulation of LPL function during infection.
Tengku-Muhammad
T S
TS
Cardiff University, Cardiff School of Biosciences, Cardiff, CF1 3US, UK.
Hughes
T R
TR
Cryer
A
A
Ramji
D P
DP
D000818:Animals; D002460:Cell Line; D003864:Depression, Chemical; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D051381:Rats
D008070:Lipopolysaccharides; D007371:Interferon-gamma; D008071:Lipoprotein Lipase