Distinct Regulatory Mechanisms for Interferon-α/β (IFN-α/β)– and IFN-γ–Mediated Induction of Ly-6E Gene in B Cells

Abstract

The murine Ly6-E gene is transcriptionally induced by interferon-α/β (IFN-α/β) and IFN-γ in a variety of distinct cell types. The mechanism of IFN inducibility in B-cell lines was investigated by deletion analysis of the promoter and by identifying DNA binding proteins in mobility shift assays. A region located in the distal part of the promoter at −2.3 kb contributed to inducibility by both types of IFNs. This region contains a novel element in addition to the previously well-characterized IFN-stimulated response element (ISRE). The probes containing ISRE detected IFN-inducible complexes in mobility shift assays and the signal transducer and activator of transcripition–1 was found to be in these complexes from cells treated with either type of IFN. An additional element present in the proximal part of the promoter at position −109 is also required for IFN-α/β–mediated induction. These data suggested a cooperative interaction between these physically disparate regulatory regions. A crucial role for HMGI(Y) protein in this cooperative multiprotein complex is supported by the evidence that inhibition of HMGI(Y) expression via antisense RNA results in the loss of IFN-α/β–mediated induction of the Ly6-E gene. These results show the complexity involved in achieving cell-type specificity in IFN-mediated gene regulation.

Cyclophosphamide Chemotherapy Sensitizes Tumor Cells to TRAIL-Dependent CD8 T Cell-Mediated Immune Attack Resulting in Suppression of Tumor Growth

“…Type-I IFN production after CY treatment was further analyzed by measuring the expression levels of Ly6AE on CD8 T cells. Ly6AE upregulation on T cells is a very early non-antigen-specific (bystander) response of T cells to IFN-exposure [27] , [28] and can therefore serve as a surrogate for type-I IFN (IFN-α/β) production. Indeed, we have recently confirmed that Ly6AE-upregulation on CD8 T cells occurs in a strictly IFN-α/β-dependent manner after AB1-HA tumor treatment with the TLR3 and TLR7 agonists poly-I:C and imiquimod [5] , [23] .…”

Cytokine Regulation and the Signaling Mechanism of Osteoclast Inhibitory Peptide-1 (OIP-1/hSca) to Inhibit Osteoclast Formation

“…(6) Ly-6 family members have been shown to be transcriptionally induced by IFNs in distinct cell types. (32) In this study, GM-CFUs were individually isolated from methyl cellulose cultures. Because of the limited numbers of GM-CFUs isolated, we used cycle-dependent RT-PCR analysis to examine the regulation of OIP-1/hSca mRNA expression in these cells.…”

Identification of the Functional Domain of Osteoclast Inhibitory Peptide-1/hSca

“…(27) Furthermore, Ly-6 family members have been shown to be induced transcriptionally by interferons in distinct cell types. (28) Interferons have been shown to inhibit osteoclastogenesis. (29,30) More recently, interferon-␥ has been shown to inhibit osteoclastogenesis through rapid degradation of TNF receptor associated factor-6 (TRAF6), which results in strong inhibition of RANKL-induced NF-B and c-Jun kinase activity.…”