Dimethyl sulfoxide modulates NF-kappa B and cytokine activation in lipopolysaccharide-treated murine macrophages

Abstract

Antioxidants are protective against septic shock in animal models. Recently, free radical scavengers have been found to inhibit the activation of the NF-KB protein in a number of cell lines. This transcriptional regulatory protein binds to the promoters of the proinflammatory cytokines tumor necrosis factor, interleukin-6, and the macrophage inflammatory proteins. The current work examined lipopolysaccharide-induced NF-KB activation in the J774 macrophage-like cell line and primary peritoneal macrophages from lipopolysaccharide-responsive (C3HeB/Fej) and -nonresponsive (C3H/HeJ) murine strains. The DNA-binding activity of the NF-KB protein directly correlated with mRNA expression for the genes encoding the proinflammatory cytokines and the free radical scavenging enzyme, superoxide dismutase. Both the p50 and p65 NF-KB subunits were detected on gel supershift assays. Minimal NF-KB activity was observed following exposure of C3H/HeJ macrophages to lipopolysaccharide. The antioxidant dimethyl sulfoxide decreased the level of NF-KB activation in the J774 cells. This correlated with decreased expression of cytokine mRNAs and tumor necrosis factor bioactivity. These results suggest that modulation of NF-KB activation may provide a mechanism through which antioxidants protect against endotoxemia in murine models.

A murine platelet-activating factor receptor gene: cloning, chromosomal localization and up-regulation of expression by lipopolysaccharide in peritoneal resident macrophages

“…Both the level and the kinetics of PAFR transcripts were comparable between these two strains. Bacterial LPS-induced TNF-α expression in C3H\HeJ macrophages was also observed ( Figure 5), although at a significantly lower level than in C3H\HeN macrophages, as has been reported previously [40,41].…”

Promoter Elements Responsible for Antioxidant Regulation of MCP-1 Gene Expression

“…As a free radical scavenger and antioxidant, DMSO has been found to inhibit the activation of the NF-àB in a number of cell lines. Kelly et al (14) reported that DMSO decreased the level of LPS-induced NF-B activation in the J774 macrophage-like cell line. DMSO also inhibited X/XO induced increases in NF-B and MCP-1 production from U937 cells (17).…”

A protective effect of pyrrolidine dithiocarbamate in a rat model of liver cirrhosis

“…Moreover, products of lipid peroxidation can modulate collagen gene expression in human fibroblasts (34, 35), and as shown recently, cytochrome P4502E1‐derived ROS induce collagen type I expression and stimulation and proliferation of rat HSC (36, 37). We demonstrated in a previous study in rats that hydroxyl radical scavengers, dimethylsulfoxide and dimethylthiourea, which inhibit NF‐kB activation in various cell types and in animal models of liver injury (38–40), prevented TAA‐induced hepatic fibrosis in vivo (41). The results of the present study of chronic treatment with TAA suggest that the inhibitory effect of PDTC on HSC activation and collagen synthesis observed in the in vivo experiments is rather indirect and probably results from reduced oxidative stress and chronic inflammatory response in the liver.…”