Role of IκBα and IκBβ in the biphasic nuclear translocation of NF-κB in TNFα-stimulated astrocytes and in neuroblastoma cells

✍ Scribed by Iris Kemler; Adriano Fontana

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 113 KB
• Volume: 26
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/(sici)1098-1136(199905)26:3<212::aid-glia3>3.0.co;2-f

✦ Synopsis

In infectious diseases of the central nervous system astrocytes respond to inflammatory cytokines like tumor necrosis factor ␣ (TNF␣) by activation of the transcription factor NF-B, mediated by the proteolysis of its inhibitors IB␣ and IB␤. We studied the kinetics of NF-B induction by TNF␣ in primary astrocytes, and in the neuroblastoma cell line Neuro2A, and compared it to fibroblasts. In the latter, NF-B DNA binding activity was induced at 30 min and remained constant up to 4 h. In contrast, in astrocytes and in Neuro2A cells NF-B DNA binding activity followed a biphasic pattern: it was induced after 30 min (early phase), declined after 1 h, and increased again at 2 to 4 h (late phase). The early phase was due to rapid degradation of IB␣. After 1 h IB␣ was resynthesized to levels exceeding the amounts present in unstimulated cells. This paralleled the low levels of nuclear NF-B binding activity. The decrease was not observed when IB␣ resynthesis was inhibited by cycloheximide. Degradation of both IB␣ and IB␤ contributed to the late phase of induction. However, the second peak occurred also in the absence of IB␤ proteolysis, demonstrating the importance of IB␣ in the formation of the biphasic nuclear translocation of NF-B.