The Effect of PD-1 Inhibitor Combined with Irradiation on HMGB1-Associated Inflammatory Cytokines and Myocardial Injury
Jie Bai,1– 3,* Bibo Wu,1– 3,* Shasha Zhao,1– 3,* Gang Wang,1– 3,* Shengfa Su,1– 3 Bing Lu,1– 3 Yinxiang Hu,1– 3 Yichao Geng,1,3 Zhengneng Guo,1– 3 Jun Wan,2,3 Weiwei OuYang,1– 3 Cheng Hu,1– 3 Jie Liu1– 3 1Department of Oncology, The Affiliated Hospital of Guizhou Medi...
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2022-11-01
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| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/the-effect-of-pd-1-inhibitor-combined-with-irradiation-on-hmgb1-associ-peer-reviewed-fulltext-article-JIR |
| _version_ | 1811303892245282816 |
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| author | Bai J Wu B Zhao S Wang G Su S Lu B Hu Y Geng Y Guo Z Wan J OuYang W Hu C Liu J |
| author_facet | Bai J Wu B Zhao S Wang G Su S Lu B Hu Y Geng Y Guo Z Wan J OuYang W Hu C Liu J |
| author_sort | Bai J |
| collection | DOAJ |
| description | Jie Bai,1– 3,* Bibo Wu,1– 3,* Shasha Zhao,1– 3,* Gang Wang,1– 3,* Shengfa Su,1– 3 Bing Lu,1– 3 Yinxiang Hu,1– 3 Yichao Geng,1,3 Zhengneng Guo,1– 3 Jun Wan,2,3 Weiwei OuYang,1– 3 Cheng Hu,1– 3 Jie Liu1– 3 1Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 3Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengfa Su, Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China, Tel +8613608550432, Fax +86513076, Email sushengfa2005@163.comPurpose: To explore the effect of PD-1 inhibitors combined with irradiation on myocardial injury and the changes of HMGB1-associated inflammatory markers.Methods: Four groups of five mice were used, each groupformed by randomly dividing 20 mice (group A control; group B PD-1 inhibitors; group C Irradiation; group D PD-1 inhibitors+irradiation; n = 5 for each). The mice were treated with either PD-1 inhibitors or a 15 Gy dose of single heart irradiation, or both. Hematoxylin-eosin staining assessed the morphology and pathology of heart tissue; Masson staining assessed heart fibrosis; Tunel staining evaluated heart apoptosis; flow cytometry detected CD3+, CD4+, and CD8+ T lymphocytes in heart tissues; enzyme linked immunosorbent assay evaluated IL-1β, IL-6, and TNF-ɑ of heart tissue; Western blot and quantitative real-time PCR (qPCR) detected the expression of protein and mRNA of HMGB1, TLR-4, and NF-κB p65 respectively.Results: The degree of heart injury, collagen volume fraction (CVF) and apoptotic index (AI) in groups B, C, and D were higher than group A, but the differences between the CVF and AI of group A and group B were not statistical significance (P> 0.05). Similarly, the absolute counts and relative percentage of CD3+ and CD8+ T lymphocytes and the concentrations of IL-1β, IL-6, and TNF-α in heart tissue with group D were significantly higher than the other groups (P< 0.05). In addition, compared with group A, the expression of protein and mRNA of HMGB1 and NF-κB p65 in other groups were higher, and the differences between each group were statistically significant while TLR4 was not. In addition, interaction by PD-1 inhibitors and irradiation was found in inflammatory indicators, especially in the expression of the HMGB1 and CD8+ T lymphocytes.Conclusion: PD-1 inhibitors can increase the expression of HMGB1-associated inflammatory cytokines and aggravate radiation-induced myocardial injury.Keywords: HMGB1, PD-1 inhibitors, radiotherapy, heart injury |
| first_indexed | 2024-04-13T07:56:18Z |
| format | Article |
| id | doaj.art-de800ae890f5446a9f255e28b9333ca5 |
| institution | Directory Open Access Journal |
| issn | 1178-7031 |
| language | English |
| last_indexed | 2024-04-13T07:56:18Z |
| publishDate | 2022-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj.art-de800ae890f5446a9f255e28b9333ca52022-12-22T02:55:24ZengDove Medical PressJournal of Inflammation Research1178-70312022-11-01Volume 156357637179766The Effect of PD-1 Inhibitor Combined with Irradiation on HMGB1-Associated Inflammatory Cytokines and Myocardial InjuryBai JWu BZhao SWang GSu SLu BHu YGeng YGuo ZWan JOuYang WHu CLiu JJie Bai,1– 3,* Bibo Wu,1– 3,* Shasha Zhao,1– 3,* Gang Wang,1– 3,* Shengfa Su,1– 3 Bing Lu,1– 3 Yinxiang Hu,1– 3 Yichao Geng,1,3 Zhengneng Guo,1– 3 Jun Wan,2,3 Weiwei OuYang,1– 3 Cheng Hu,1– 3 Jie Liu1– 3 1Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 3Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengfa Su, Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China, Tel +8613608550432, Fax +86513076, Email sushengfa2005@163.comPurpose: To explore the effect of PD-1 inhibitors combined with irradiation on myocardial injury and the changes of HMGB1-associated inflammatory markers.Methods: Four groups of five mice were used, each groupformed by randomly dividing 20 mice (group A control; group B PD-1 inhibitors; group C Irradiation; group D PD-1 inhibitors+irradiation; n = 5 for each). The mice were treated with either PD-1 inhibitors or a 15 Gy dose of single heart irradiation, or both. Hematoxylin-eosin staining assessed the morphology and pathology of heart tissue; Masson staining assessed heart fibrosis; Tunel staining evaluated heart apoptosis; flow cytometry detected CD3+, CD4+, and CD8+ T lymphocytes in heart tissues; enzyme linked immunosorbent assay evaluated IL-1β, IL-6, and TNF-ɑ of heart tissue; Western blot and quantitative real-time PCR (qPCR) detected the expression of protein and mRNA of HMGB1, TLR-4, and NF-κB p65 respectively.Results: The degree of heart injury, collagen volume fraction (CVF) and apoptotic index (AI) in groups B, C, and D were higher than group A, but the differences between the CVF and AI of group A and group B were not statistical significance (P> 0.05). Similarly, the absolute counts and relative percentage of CD3+ and CD8+ T lymphocytes and the concentrations of IL-1β, IL-6, and TNF-α in heart tissue with group D were significantly higher than the other groups (P< 0.05). In addition, compared with group A, the expression of protein and mRNA of HMGB1 and NF-κB p65 in other groups were higher, and the differences between each group were statistically significant while TLR4 was not. In addition, interaction by PD-1 inhibitors and irradiation was found in inflammatory indicators, especially in the expression of the HMGB1 and CD8+ T lymphocytes.Conclusion: PD-1 inhibitors can increase the expression of HMGB1-associated inflammatory cytokines and aggravate radiation-induced myocardial injury.Keywords: HMGB1, PD-1 inhibitors, radiotherapy, heart injuryhttps://www.dovepress.com/the-effect-of-pd-1-inhibitor-combined-with-irradiation-on-hmgb1-associ-peer-reviewed-fulltext-article-JIRhmgb1pd-1 inhibitorsradiotherapyheart injury |
| spellingShingle | Bai J Wu B Zhao S Wang G Su S Lu B Hu Y Geng Y Guo Z Wan J OuYang W Hu C Liu J The Effect of PD-1 Inhibitor Combined with Irradiation on HMGB1-Associated Inflammatory Cytokines and Myocardial Injury Journal of Inflammation Research hmgb1 pd-1 inhibitors radiotherapy heart injury |
| title | The Effect of PD-1 Inhibitor Combined with Irradiation on HMGB1-Associated Inflammatory Cytokines and Myocardial Injury |
| title_full | The Effect of PD-1 Inhibitor Combined with Irradiation on HMGB1-Associated Inflammatory Cytokines and Myocardial Injury |
| title_fullStr | The Effect of PD-1 Inhibitor Combined with Irradiation on HMGB1-Associated Inflammatory Cytokines and Myocardial Injury |
| title_full_unstemmed | The Effect of PD-1 Inhibitor Combined with Irradiation on HMGB1-Associated Inflammatory Cytokines and Myocardial Injury |
| title_short | The Effect of PD-1 Inhibitor Combined with Irradiation on HMGB1-Associated Inflammatory Cytokines and Myocardial Injury |
| title_sort | effect of pd 1 inhibitor combined with irradiation on hmgb1 associated inflammatory cytokines and myocardial injury |
| topic | hmgb1 pd-1 inhibitors radiotherapy heart injury |
| url | https://www.dovepress.com/the-effect-of-pd-1-inhibitor-combined-with-irradiation-on-hmgb1-associ-peer-reviewed-fulltext-article-JIR |
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