Regulation of Inducible Nitric Oxide Synthase mRNA Levels by LPS, INF-γ, TGF-β, and IL-10 in Murine Macrophage Cell Lines and Rat Peritoneal Macrophages

The molecular mechanisms of LPS, INF-γ, TGF-β, and IL-10 regulation of inducible nitric oxide synthase (iNOS) mRNA expression were evaluated. In murine macrophage cell lines, LPS-induced increases in iNOS mRNA were blocked by either cycloheximide or actinomycin D. Neither TGF-β nor IL-10 alone had any effect on basal expression, and each only slightly reduced LPS induction of iNOS mRNA. However, IL-10 augmented INF-γ induction of iNOS mRNA to very high levels, while TGF-β inhibited INF-γ induction. Human monocytes expressed no detectable iNOS mRNA with any stimuli, though Southern analysis on human genomic DNA revealed a specific human iNOS gene. In human macrophages, the iNOS gene may have become inoperative during evolution.