Interleukin-17 stimulates the expression of IkappaB alpha mRNA and the secretion of IL-6 and IL-8 in glioblastoma cell lines.
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)-kappaB, which is being discussed as one of the most important transcription factors in the regulation of neuronal and glial cell function. Activation of NF-kappaB involves the degradation of its cytoplasmatic inhibitor IkappaB-alpha, which allows the nuclear translocation of NF-kappaB, and ensures transcriptional activation of genes including IkappaB-alpha itself. Using a competitive RT-PCR, we examined the IL-17-induced IkappaB-alpha mRNA expression in glioblastoma cells, and we examined IL-17 up-regulated IkappaB-alpha 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 (protein kinase C inhibitor) and genistein (tyrosine kinase inhibitor). After 60 min of IL-17 stimulation, a degradation of the IkappaB-alpha protein was detectable. Furthermore, IL-17 stimulated the secretion of IL-6 and IL-8 in glial cells, and IL-17 and IL-1beta 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.
Kehlen
A
A
Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Germany. astrid.kehlen@medizin.uni-halle.de
Thiele
K
K
Riemann
D
D
Rainov
N
N
Langner
J
J
D004268:DNA-Binding Proteins / Q000235:genetics*; D005909:Glioblastoma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D020672:I-kappa B Proteins; D020381:Interleukin-17 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D012333:RNA, Messenger / Q000032:analysis*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha