Abnormal Nuclear Factor (NF)-κB Signal Pathway and Aspirin Inhibits Tumor Necrosis Factor α–Induced NF-κB Activation in Keloid Fibroblasts

BACKGROUND: Keloid is characterized with disproportionate extracellular matrix accumulation and fibroblast proliferation. Rel/nuclear factor-kappaB (NF-kappaB) signal transduction pathway may play an important role in keloid pathogenesis. OBJECTIVE: To examine the effect of aspirin on the tumor necrosis factor (TNF)-alpha-induced NF-kappaB activation in keloid fibroblasts. METHODS: Primary cultured fibroblasts were pretreated with aspirin and then stimulated with TNF-alpha. Proliferation and apoptosis were measured by MTT reduction and flow cytometry. Expression of DNA-binding activity of NF-kappaB p65 and cytoplasmic IkappaBalpha/p- IkappaBalpha protein levels were determined by Trans AM NF-kappaB/p65 kit and Western blot, respectively. Subcellular localization of NF-kappaB p65 and IkappaBalpha were observed with immunofluorescence assay. RESULTS: In this study, we demonstrate that TNF-alpha induced NF-kappaB activation in keloid fibroblasts, which show more sensitively than the normal skin fibroblasts. Aspirin pretreatment can inhibit TNF-alpha-induced activation of NF-kappaB in a dose-dependent manner by preventing the phosphorylation and degradation of IkappaBalpha and nuclear translocation of NF-kappaB. Moreover, aspirin may inhibit keloid fibroblasts proliferation and sensitize keloid fibroblasts to apoptosis. CONCLUSION: These results suggest that aspirin could help in developing therapeutic interventions for the treatment of keloid scarring.