Despite efforts to develop efficient chemotherapeutic drug strategies to treat cancer, acquired drug resistance is a commonly encountered problem. In the present study, to investigate this phenomenon, human A549 lung cancer cells resistant to the topoisomerase inhibitor etoposide (A549RT‑eto) were used and compared with A549 parental cells. A549RT‑eto cells demonstrated increased resistance to ...

Proper regulation of the Tap-1 gene is critical for the initiation and continuation of a cellular immune response. Analysis of the Tap-1/low molecular mass polypeptide 2 bidirectional promoter showed that the IFN-gamma activation site element is critical for the rapid induction of the promoter by IFN-gamma following transfection into the human macrophage cell line THP-1. Furthermore, activation...

Type I IFNs induce gene expression through Stat1 and Stat2, which can in turn associate either to form Stat1 homodimers or the transcription factor ISGF-3. Stat1 homodimers also transduce signals for IFN-gamma. To explore the unique properties of Stat2 and ISGF-3 in type I IFN signaling, its gene was targeted for deletion. Stat2 null mice exhibit a number of defects in immune response. This inc...

Atherosclerotic plaque development involves multiple extra- and intra-cellular signals engaging cells from the immune system and from the vasculature. Pro-inflammatory pathways activated by interferon gamma (IFNγ) and toll-like receptor 4 (TLR4) ligands are profoundly involved in plaque formation and have been shown to involve cross-talk in all atheroma-interacting cell types leading to increas...

Signal transducers and activators of transcription (STATs) can transduce cytokine signals and regulate gene expression. The cellular localization and nuclear trafficking of STAT1, a representative of the STAT family with multiple transcriptional functions, is tightly related with transcription process, which usually happens in the interphase of the cell cycle. However, these priority questions ...

Gene regulation by cytokine-activated transcription factors of the signal transducer and activator of transcription (STAT) family requires serine phosphorylation within the transactivation domain (TAD). STAT1 and STAT3 TAD phosphorylation occurs upon promoter binding by an unknown kinase. Here, we show that the cyclin-dependent kinase 8 (CDK8) module of the Mediator complex phosphorylated regul...

Host defense against the parasite Toxoplasma gondii requires the cytokine interferon-gamma (IFNγ). However, Toxoplasma inhibits the host cell transcriptional response to IFNγ, which is thought to allow the parasite to establish a chronic infection. It is not known whether all strains of Toxoplasma block IFNγ-responsive transcription equally and whether this inhibition occurs solely through the ...

The pathological role of interferon-g (IFN-g) in atherosclerosis is mediated through effects on macrophages, foam cells, and other vascular cells. Recently, we reported that ABC1 message and protein levels were decreased 3to 4-fold in foam cells by IFN-g. In the present study, the pathway by which IFN-g inhibited ABC1 expression was investigated with Stat1 knockout mice. IFN-g–stimulated, wild-...

Signal transducer and activator of transcription (Stat), a family of transcriptional factors, has been demonstrated to play a critical role in gene regulation in response to inflammatory cytokines, such as interferon and interleukin-6. Inflammatory cytokines and bacterial endotoxin are known to suppress, in most of cases, the constitutive or induced cytochromes P450 (P450) in animals and humans...