Interleukin-1 beta uses common and distinct signaling pathways for induction of the interleukin-6 and tumor necrosis factor alpha genes in the human astrocytoma cell line U373.
Cytokines are involved in the etiology of different disorders of the CNS. For a better understanding of their pathogenic role, we analyzed signal transduction pathways mediating the interleukin (IL)-1 beta-induced synthesis of IL-6 and tumor necrosis factor alpha (TNF alpha) in the human astrocytoma cell line U373 MG. Both protein kinase C and reactive oxygen intermediates (ROIs) were involved in IL-6 and TNF alpha gene expression by IL-1 beta. In contrast, protein tyrosine kinases were only necessary for expression of the IL-6 gene. Whereas activation of protein kinase A was able to induce expression of the IL-6 gene, it did not induce TNF alpha gene expression and was not involved in IL-1 beta-induced IL-6 and TNF alpha gene expression. Activation of the transcription factor nuclear factor-kappa B by IL-1 beta involved ROIs, whereas the IL-1 beta-induced activation of the transcription factor AP-1 was mediated via protein kinase C. Our findings provide the basis for the development of specific drugs for the treatment of disorders of the CNS in which cytokines play a pathogenic role.
Lieb
K
K
Psychiatrische und Psychosomatisch Klinik, Universität Freiburg, Germany.
Kaltschmidt
C
C
Kaltschmidt
B
B
Baeuerle
P A
PA
Berger
M
M
Bauer
J
J
Fiebich
B L
BL
D001254:Astrocytoma / Q000201:enzymology / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C