Interleukin-17 stimulates the expression of IκBα mRNA and the secretion of IL-6 and IL-8 in glioblastoma cell lines

• Published in: Journal of neuroimmunology 1999-11, Vol.101 (1), p.1-6
• Main Authors: Kehlen, A, Thiele, K, Riemann, D, Rainov, N, Langner, J
• Format: Article
• Language: English
• Subjects: glioblastoma; glioblastoma cells; I^KB^a protein; IBa protein; Inflammation; Interleukin-17; Interleukins; IκB-α; Neurodegenerative diseases; NF-^KB protein; NF-B protein; NF-κB
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(99)00111-3

Interleukin-17 (IL-17) has been characterized as a proinflammatory cytokine produced by CD4 + activated memory T cells. In an effort to elucidate the biological effects of IL-17 in glial cells, we investigated the ability of this cytokine in order to activate nuclear factor (NF)-κB, which is being discussed as one of the most important transcription factors in the regulation of neuronal and glial cell function. Activation of NF-κB involves the degradation of its cytoplasmatic inhibitor IκB-α, which allows the nuclear translocation of NF-κB, and ensures transcriptional activation of genes including IκB-α itself. Using a competitive RT-PCR, we examined the IL-17-induced IκB-α mRNA expression in glioblastoma cells, and we examined IL-17 up-regulated IκB-α mRNA expression in a dose- and time-dependent fashion with a maximum time between 1 and 3 h. This induction could be inhibited by Calphostin C (proteinkinase C inhibitor) and genistein (tyrosine kinase inhibitor). After 60 min of IL-17 stimulation, a degradation of the IκB-α protein was detectable. Furthermore, IL-17 stimulated the secretion of IL-6 and IL-8 in glial cells, and IL-17 and IL-1β in combination showed a superadditive effect. We suggest IL-17 to play a role as an immune factor, possibly involved in complex pathophysiological interactions of neurodegenerative diseases.