DEPENDENCE AND REVERSAL OF NITRIC-OXIDE PRODUCTION ON NF-KAPPA-B IN SILICA AND LIPOPOLYSACCHARIDE-INDUCED MACROPHAGES

In this report the differential regulation of NF-kappa B and nitric oxide (NO) was investigated in the mouse macrophage cell line RAW 264.7 following exposure to a mineral dust (silica) and/or an endotoxin (Lipopolysaccharide, LPS). The results indicated that silica and LPS can significantly induce the activation of NF-kappa B as well as elicit enhanced production of NO in RAW 264.7 cells as part of an early inflammatory response mechanism. A 24-hour time-course study showed that NO release from these cells continued to increase following the initial stimulus by LPS or silica. In contrast, activation of NF-kappa B was maximal at 6 hours and then showed a steady decline to 24 hours. The production of NO was suppressed by protease inhibitor and antioxidant, both of which block the activation of NF-kappa B. Surprisingly, the use of an NO synthase inhibitor resulted in an enhancement of NF-kappa B activation. These findings suggest that NO produced in macrophage cells in response to an inflammatory stimulus like silica or LPS my be linked to a negative feedback role on the activation of NF-kappa B. (C) 1995 Academic Press, Inc.