Differential induction of interferon (IFN)-inducible protein 10 following differentiation of a monocyte, macrophage cell lineage is related to the changes of nuclear proteins bound to IFN stimulus response element and kappa B sites

We examined chemokine gene expression following the differentiation of a mo nocyte, macrophage cell lineage. The human monoblastic cell line, U937 was differentiated to macrophages by the treatment with either phorbol 12-myris tate 13-acetate (PMA), retinoic acid (RA), or vitamin D3 (VitD3). The gene expression of interferon (IFN)-inducible protein 10 (IP-10) (a CXC chemokin e) was markedly augmented by the IFN gamma treatment in PMA- or RA-differen tiated U937 cells, but only marginally in undifferentiated or VitD3-treated cells. In contrast, another inducible gene expression of monocyte chemotac tic protein-1 (a CC chemokine) and the activation of the transcriptional fa ctor (FcRF gamma) bound to the gamma response region were similarly or less abundantly induced by IFN gamma treatment in PMA- or RA-differentiated U93 7 cells, indicating that increased IP-10 mRNA induction was not due to the augmented ability of the cells to respond to the presence of IFN I. Increas ed expression of IFN gamma-induced IP-10 mRNA following the differentiation of U937 cells was mediated largely by augmented transcriptional activity o f the gene and was related to differentiation-dependent changes of the prot eins bound to IFN stimulus response element (ISRE) and KB sites, suggesting that these 'constitutive' nuclear proteins may determine the IP-10 mRNA in ducibility by IFN gamma.