Maleylated-BSA Enhances Production of Nitric Oxide from Macrophages

• Published in: Biochemical and biophysical research communications 1998-04, Vol.245 (1), p.185-189
• Main Authors: Alford, Paul B., Xue, Yan, Thai, Sheau-Fung, Shackelford, Rodney E.
• Format: Article
• Language: English
• Subjects: Animals; DNA-Binding Proteins - analysis; Gene Expression Regulation, Enzymologic - genetics; Interferon-gamma - pharmacology; Lipoproteins, LDL - pharmacology; Macrophages, Peritoneal - metabolism; Mice; Mice, Inbred Strains; NF-kappa B - metabolism; Nitric Oxide - metabolism; Promoter Regions, Genetic - genetics; RNA, Messenger - metabolism; Serum Albumin, Bovine - pharmacology; Transcription, Genetic - genetics
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1998.8400

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-γ (INF-γ) 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-κB dimers capable of binding the NF-κBd 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-γ failed to demonstrate synergy at the transcriptional or mRNA levels, as these levels were comparable to those elicited by IFN-γ alone. These studies suggest that the synergy in NO production between maleyl-BSA and IFN-γ occurs after the accumulation of iNOS-specific mRNA, possibly at the translational or post-translational level.