CXC ligand 10 (CXCL10) and CXCL9 are chemoattractants for activated T cells and possess angiostatic activity. Both CXCL9 and CXCL10 have been considered as important components for the anti-tumour activities of interferon-γ (IFNγ) and interleukin-12 in animal models. In this article we show that the CXCL9 and CXCL10 genes in some types of human tumour cell lines are not inducible by IFNγ and we describe experiments designed to explore the molecular mechanisms involved in this impaired induction. The human oral squamous carcinoma line Ca9-22 and the glioma line A172 failed to express CXCL9 and CXCL10 mRNAs in response to IFNγ, whereas other carcinoma lines including HSC-2 did express these mRNAs. Production of these chemokine proteins was also impaired in Ca9-22 cells. The impaired expression was not due to any deficiency in the IFNγ/signal transducer and activator of transcription 1 (STAT1)-dependent signalling pathway. Instead, analysis of nuclear factor κB (NF-κB) activity revealed that the constitutive low level of NF-κB activity, which is seen in cells that express these chemokines, was absent in Ca9-22 and A172 cells. Activation of NF-κB in Ca9-22 cells restored the expression of IFNγ-stimulated CXCL9 and CXCL10 mRNAs. In contrast, inhibition of the constitutive NF-κB in HSC-2 cells by adenovirus-mediated gene transfer of a dominant-negative IκBα suppressed the IFNγ-induced expression of the CXCL9 and CXCL10 mRNAs. These results indicate that constitutive NF-κB activity, which is often associated with tumour development, is required for the induced expression of CXCL9 and CXCL10 genes in human tumour cell lines in response to IFNγ.
Constitutive nuclear factor κB activity is required to elicit interferon-γ-induced expression of chemokine CXC ligand 9 (CXCL9) and CXCL10 in human tumour cell lines
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Miki HIROI, Yoshihiro OHMORI; Constitutive nuclear factor κB activity is required to elicit interferon-γ-induced expression of chemokine CXC ligand 9 (CXCL9) and CXCL10 in human tumour cell lines. Biochem J 1 December 2003; 376 (2): 393–402. doi: https://doi.org/10.1042/bj20030842
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