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http://dx.doi.org/10.7845/kjm.2013.3082

PD-1 Expression in LPS-Induced Raw264.7 Cells Is Regulated via Co-activation of Transcription Factor NF-κB and IRF-1  

Choi, Eun-Kyoung (Department of Microbiology, Advanced Research Center for Multiple Myeloma, College of Medicine, Inje University)
Lee, Soo-Woon (Department of Oral and Maxillofacial Surgery, Haeundae Paik Hospital, Inje University)
Lee, Soo-Woong (Department of Microbiology, Advanced Research Center for Multiple Myeloma, College of Medicine, Inje University)
Publication Information
Korean Journal of Microbiology / v.49, no.4, 2013 , pp. 301-308 More about this Journal
Abstract
Programmed Death-1 (PD-1) is one of the important immune-inhibitory molecules which was expressed in T cells, B cells, NKT cells, and macrophages activated by various immune activating factors. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is one of the crucial immunogens for PD-1 expression. However, there are only a few reports on the expression mechanisms of PD-1 in innate immune cells. In this study, we investigate the expression mechanisms of PD-1 in LPS-stimulated Raw264.7 cell lines by RT-PCR, Western Blot, flow cytometry as well as ChIP assay and co-immunoprecipitation. When Raw264.7 cells were stimulated with LPS, PD-1 expression was greatly up-regulated via PI3K and p38 signaling. Primary macrophages isolated from LPS-injected mice were also shown the increased expression of PD-1. In promoter assay, NF-${\kappa}B$ and IRF-1 binding regions in mouse PD-1 promoter are important for PD-1 expression. We also found that the co-activation of NF-${\kappa}B$ and IRF-1 is indispensable for the maximum PD-1 expression. These results indicate that the modulation of PD-1 expressed in innate immune cells could be a crucial for the disease therapy such as LPS-induced mouse sepsis model.
Keywords
IRF-1; lipopolysaccharide; NF-${\kappa}B$; programmed Death-1; Raw264.7;
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