| Autor: |
Liu, Peng, Ye, Lichun, Ren, Yongshen, Zhao, Guodun, Zhang, Yun, Lu, Shaojuan, Li, Qiang, Wu, Chen, Bai, Lijie, Zhang, Zhongyun, Zhao, Zhongqiu, Shi, Zhaohua, Yin, Shijin, Liao, Maochuan, Lan, Zhou, Feng, Jing, Chen, Lvyi |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology; Apr2023, Vol. 180 Issue 8, p1132-1147, 16p, 6 Graphs |
| Abstrakt: |
Background and Purpose: Intravenous infusion of chemotherapy drugs can cause severe chemotherapy‐induced phlebitis (CIP) in patients. However, the underlying mechanism of CIP development remains unclear. Experimental Approach: RNA‐sequencing analysis was used to identify potential disease targets in CIP. Guanylate binding protein‐5 (GBP5) genetic deletion approaches also were used to investigate the role of GBP5 in NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in lipopolysaccharide (LPS) primed murine bone‐marrow‐derived macrophages (BMDMs) induced by vinorelbine (VIN) in vitro and in mouse models of VIN‐induced CIP in vivo. The anti‐CIP effect of aescin was evaluated, both in vivo and in vivo. Key Results: Here, we show that the expression of GBP5 was upregulated in human peripheral blood mononuclear cells from CIP patients. Genetic ablation of GBP5 in murine macrophages significantly alleviated VIN‐induced CIP in the experimental mouse model. Mechanistically, GBP5 contributed to the inflammatory responses through activating NLRP3 inflammasome and driving the production of the inflammatory cytokine IL‐1β. Moreover, aescin, a mixture of triterpene saponins extracted from horse chestnut seed, can alleviate CIP by inhibiting the GBP5/NLRP3 axis. Conclusion and Implications: These findings suggest that GBP5 is an important regulator of NLRP3 inflammasome in CIP mouse model. Our work further reveals that aescin may serve as a promising candidate in the clinical treatment of CIP. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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