Abnormal nuclear factor (NF)-kappa B signal pathway and aspirin inhibits tumor necrosis factor alpha-induced NF-kappa B activation in keloid fibroblasts

作者：Zhu, Guiying; Cai, Jinglong^*; Zhang, Jie; Zhao, Yueran; Xu, Bin

来源：Dermatologic Surgery, 2007, 33(6): 697-708.

DOI：10.1111/j.1524-4725.2007.33146.x

• COLON-CANCER CELLS
• MEDIATED APOPTOSIS
• GENES
• PROLIFERATION
• EXPRESSION
• MECHANISM
• GROWTH

Background Keloid is characterized with disproportionate extracellular matrix accumulation and fibroblast proliferation. Rel/nuclear factor-kappaB (NF-kappa B) 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-kappa B 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-kappa B p65 and cytoplasmic I kappa B alpha/p- I kappa B alpha protein levels were determined by Trans AM NF-kappa B/p65 kit and Western blot, respectively. Subcellular localization of NF-kappa B p65 and I kappa B alpha were observed with immunofluorescence assay.
Results In this study, we demonstrate that TNF-alpha induced NF-kappa B activation in keloid fibroblasts, which show more sensitively than the normal skin fibroblasts. Aspirin pretreatment can inhibit TNF-alpha-induced activation of NF-kappa B in a dose-dependent manner by preventing the phosphorylation and degradation of I kappa B alpha and nuclear translocation of NF-kappa B. Moreover, aspirin may inhibit keloid fibroblasts proliferation and sensitize keloid fibroblasts to apoptosis.
Conclusions These results suggest that aspirin could help in developing therapeutic interventions for the treatment of keloid scarring.

• 出版日期2007-6
• 单位山东省立医院; 山东大学