Maleylated-BSA enhances production of nitric oxide from macrophages.
Maleylated-bovine serum albumin (maleyl-BSA) elicits transcription and secretion of a number of proinflammatory genes via ligation of the low-affinity scavenger receptor (SR) on macrophages. We now demonstrate that while neither maleyl-BSA, nor interferon-gamma (INF-gamma) alone induce nitric oxide (NO) production, when combined they promote release of NO from murine peritoneal macrophages. This effect was blocked by treatment with oxidized-low density lipoprotein. Maleyl-BSA activated NF-kappaB dimers capable of binding the NF-kappaBd sequence unique to the iNOS promoter, but this failed to induce significant new transcription or accumulation of iNOS mRNA. The combination of maleyl-BSA and IFN-gamma failed to demonstrate synergy at the transcriptional or mRNA levels, as these levels were comparable to those elicited by IFN-gamma alone. These studies suggest that the synergy in NO production between maleyl-BSA and IFN-gamma occurs after the accumulation of iNOS-specific mRNA, possibly at the translational or post-translational level.
Alford
P B
PB
Department of Pathology, Duke University Medical Center, Durham, North Carolina, 27708, USA.
Xue
Y
Y
Thai
S F
SF
Shackelford
R E
RE
D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D012333:RNA, Messenger; C049877:maleylalbumin; C099252:oxidized low density lipoprotein; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D007371:Interferon-gamma