BACKGROUND AND OBJECTIVE: Carbon monoxide releasing molecule-3 (CORM-3) is a newly reported compound that has shown anti-inflammatory effects in a number of cells. In this study, we aimed to investigate the influence of CORM-3 on concurrent tumor necrosis factor-α (TNF-α)- and interleukin (IL)-1β-induced expression of adhesion molecules on human gingival fibroblasts (HGF). MATERIAL AND METHODS: HGF were cultured from the explants of normal gingival tissues. Cells were costimulated with TNF-α and IL-1β in the presence or absence of CORM-3 for different periods of time. The expression of adhesion molecules, nuclear factor-kappaB (NF-κB) and phosphorylated p38 was studied using western blotting. RT-PCR was applied to check the expression of the adhesion molecules at the mRNA level. The activity of NF-κB was analysed using a reporter gene assay. RESULTS: CORM-3 inhibited the up-regulation of intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule in HGF after costimulation with TNF-α and IL-1β, which resulted in the decreased adhesion of peripheral blood mononuclear cells to these cells. Sustained activation of the NF-κB pathway by costimulation with TNF-α and IL-1β was suppressed by CORM-3, which was reflected by a reduced NF-κB response element-dependent luciferase activity and decreased nuclear NF-κB-p65 expression. CORM-3 inhibited MAPK p38 phosphorylation in response to stimulation with proinflammatory cytokines. CONCLUSION: The results of this study bode well for the application of CORM-3 as an anti-inflammatory agent to inhibit NF-κB activity and to suppress the expression of adhesion molecules on HGF, which suggests a promising potential for CORM-3 in the treatment of inflammatory periodontal disease.
BACKGROUND AND OBJECTIVE:Carbon monoxide releasing molecule-3 (CORM-3) is a newly reported compound that has shown anti-inflammatory effects in a number of cells. In this study, we aimed to investigate the influence of CORM-3 on concurrent tumor necrosis factor-α (TNF-α)- and interleukin (IL)-1β-induced expression of adhesion molecules on human gingival fibroblasts (HGF). MATERIAL AND METHODS:HGF were cultured from the explants of normal gingival tissues. Cells were costimulated with TNF-α and IL-1β in the presence or absence of CORM-3 for different periods of time. The expression of adhesion molecules, nuclear factor-kappaB (NF-κB) and phosphorylated p38 was studied using western blotting. RT-PCR was applied to check the expression of the adhesion molecules at the mRNA level. The activity of NF-κB was analysed using a reporter gene assay. RESULTS: CORM-3 inhibited the up-regulation of intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule in HGF after costimulation with TNF-α and IL-1β, which resulted in the decreased adhesion of peripheral blood mononuclear cells to these cells. Sustained activation of the NF-κB pathway by costimulation with TNF-α and IL-1β was suppressed by CORM-3, which was reflected by a reduced NF-κB response element-dependent luciferase activity and decreased nuclear NF-κB-p65 expression. CORM-3 inhibited MAPK p38 phosphorylation in response to stimulation with proinflammatory cytokines. CONCLUSION: The results of this study bode well for the application of CORM-3 as an anti-inflammatory agent to inhibit NF-κB activity and to suppress the expression of adhesion molecules on HGF, which suggests a promising potential for CORM-3 in the treatment of inflammatory periodontal disease.