Naschberger E, Stürzl M (2004)
Publication Type: Journal article
Publication year: 2004
Book Volume: 379
Pages Range: 409-420
Journal Issue: 2
DOI: 10.1042/BJ20031873
The large GTPase GBP-1 (guanylate-binding protein -1) is a major IFN-γ (interferon-γ)-induced protein with potent anti-angiogenic activity in endothelial cells. An ISRE (IFN-α-stimulated response element) is necessary and sufficient for the induction of GBP-1 expression by IFN-γ. Recently, we have shown that in vivo GBP-1 expression is strongly endothelial-cell-associated and is, in addition to IFN-γ, also activated by interleukin-1β and tumour necrosis factor-α, both in vitro and in vivo [Lubeseder-Martellato, Guenzi, Jörg, Töpolt, Naschberger, Kremmer, Zietz, Tschachler, Hutzler, Schwemmle et al. (2002) Am. J. Pathol. 161, 1749-1759; Guenzi, Töpolt, Cornali, Lubeseder-Martellato, Jörg, Matzen, Zietz, Kremmer, Nappi, Schwemmle et al. (2001) EMBO J. 20, 5568-5577]. In the present study, we identified a NF-κB (nuclear factor κB)-binding motif that, together with ISRE, is required for the induction of GBP-1 expression by interleukin-1β and tumour necrosis factor-α. Deactivation of the NF-κB motif reduced the additive effects of combinations of these cytokines with IFN-γ by more than 50%. Importantly, NF-κB p50 rather than p65 activated the GBP-1 promoter. The NF-κB motif and ISRE were detected in an almost identical spatial organization, as in the GBP-1 promoter, in the promoter regions of various inflammation-associated genes. Therefore both motifs may constitute a cooperative inflammatory cytokine response module that regulates GBP-1 expression. Our findings may open new perspectives for the use of NF-κB inhibitors to support angiogenesis in inflammatory diseases including ischaemia.
APA:
Naschberger, E., & Stürzl, M. (2004). Nuclear factor-κB motif and interferon-α-stimulated response element co-operate in the activation of guanylate-binding protein-1 expression by inflammatory cytokines in endothelial cells. Biochemical Journal, 379(2), 409-420. https://doi.org/10.1042/BJ20031873
MLA:
Naschberger, Elisabeth, and Michael Stürzl. "Nuclear factor-κB motif and interferon-α-stimulated response element co-operate in the activation of guanylate-binding protein-1 expression by inflammatory cytokines in endothelial cells." Biochemical Journal 379.2 (2004): 409-420.
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