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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
Peer-reviewed Journal Articles, etc >
Regulation of programmed death ligand 1 expression by interferon-gamma and tumour necrosis factor-alpha in canine tumour cell lines
| Title: | Regulation of programmed death ligand 1 expression by interferon-gamma and tumour necrosis factor-alpha in canine tumour cell lines |
| Authors: | Owaki, Ryo Browse this author | | Deguchi, Tatsuya Browse this author →KAKEN DB | | Konnai, Satoru Browse this author →KAKEN DB | | Maekawa, Naoya Browse this author →KAKEN DB | | Okagawa, Tomohiro Browse this author →KAKEN DB | | Hosoya, Kenji Browse this author →KAKEN DB | | Kim, Sangho Browse this author | | Sunaga, Takafumi Browse this author →KAKEN DB | | Okumura, Masahiro Browse this author |
| Keywords: | cell signalling | | immunology | | in vitro models | | oncology | | small animal |
| Issue Date: | 25-May-2023 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Veterinary and comparative oncology |
| Publisher DOI: | 10.1111/vco.12886 |
| Abstract: | Expression of programmed death ligand 1 (PD-L1) on tumour cells provides an immune evasion mechanism by inducing suppression of cytotoxic T cells. Various regulatory mechanisms of PD-L1 expression have been described in human tumours, however, little is known in canine tumours. To investigate whether inflammatory signalling is involved in PD-L1 regulation in canine tumours, the effects of interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha treatment were examined in canine malignant melanoma cell lines (CMeC and LMeC) and an osteosarcoma cell line (HMPOS). The protein level of PD-L1 expression was upregulated by IFN-gamma and TNF-alpha stimulation. Upon IFN-gamma stimulation, all cell lines showed an increase in expression of PD-L1, signal transducer and activator of transcription (STAT)1, STAT3 and genes regulated by STAT activation. Upregulated expression of these genes was suppressed by the addition of a JAK inhibitor, oclacitinib. Contrastingly, upon TNF-alpha stimulation, all cell lines exhibited higher gene expression of the nuclear factor kappa B (NF-kappa B) gene RELA and genes regulated by NF-kappa B activation, whereas expression of PD-L1 was upregulated in LMeC only. Upregulated expression of these genes was suppressed by the addition of an NF-kappa B inhibitor, BAY 11-7082. The expression level of cell surface PD-L1 induced by IFN-gamma and TNF-alpha treatment was reduced by oclacitinib and BAY 11-7082, respectively, indicating that upregulation of PD-L1 expression by IFN-gamma and TNF-alpha stimulation is regulated via the JAK-STAT and NF-kappa B signalling pathways, respectively. These results provide insights into the role of inflammatory signalling in PD-L1 regulation in canine tumours. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/89335 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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