Abnormal nuclear factor (NF)-kappaB signal pathway and aspirin inhibits tumor necrosis factor alpha-induced NF-kappaB 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.


CONCLUSIONS
These results suggest that aspirin could help in developing therapeutic interventions for the treatment of keloid scarring.
Zhu
Guiying
G
Department of Plastic Surgery, The Second Hospital of Shandong University, Jinan, Shandong Province, People's Republic of China.
Cai
Jinglong
J
Zhang
Jie
J
Zhao
Yueran
Y
Xu
Bin
B
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007627:Keloid / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D001241:Aspirin