Regulation of macrophage TNF alpha, IL-1 beta, and Ia (I-A alpha) mRNA expression during peritonitis is site dependent.
Failure of the immune system to successfully prevent organ failure after injury or infection may be associated with a shift in macrophage function from antigen recognition and presentation to overexpression of inflammatory cytokines. Regulation may be due to changes in macrophage gene expression. Levels of mRNA for tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and the Ia subunit, I-A alpha, in peritoneal macrophages, liver, spleen, kidney, and lung were measured following cecal ligation and puncture (CLP) in Swiss Webster mice. Northern blot analysis was performed using 32P-labeled mouse cDNA probes. Peritoneal macrophage TNF alpha and IL-1 beta mRNA expression increased 2.5- and 2-fold, respectively, by 6 hr after CLP and remained elevated at 24 hr. Peritoneal macrophage I-A alpha mRNA levels decreased 8-fold by 24 hr after CLP. I-A alpha mRNA expression in liver, spleen, kidney, and lung decreased following CLP, with a return toward normal levels by 8 days in all tissues except spleen. IL-1 beta and TNF alpha mRNA were barely detectable in liver and kidney. IL-1 beta mRNA tended to increase over time in lung and spleen, whereas TNF alpha mRNA in these tissues did not vary greatly after CLP. Muramyl dipeptide or monophosphoryl lipid A pretreatment of animals prior to CLP was ineffective in altering the expression of TNF alpha and I-A alpha mRNA. We conclude that peritonitis is associated with an early increase in peritoneal macrophage TNF alpha and IL-1 beta mRNA levels and a sharp decline in macrophage I-A alpha mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
McMasters
K M
KM
Department of Surgery, University of Louisville School of Medicine, Kentucky 40292.
Cheadle
W G
WG
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000818:Animals; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007375:Interleukin-1 / Q000235:genetics*; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D010538:Peritonitis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D008050:Lipid A; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C048436:monophosphoryl lipid A