RU.521 protects against neutrophil extracellular traps-induced vascular endothelial injury by inhibiting cGAS/STING pathway

Authors

  • Biao Zhang Department of Central Laboratory, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, China.
  • Zaojun Fang Department of Emergency, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, China.
  • Ying Lin Department of Emergency, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, China.
  • Qian Wu Department of Central Laboratory, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, China.
  • Jiaping Chen Department of Emergency, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, China.

DOI:

https://doi.org/10.3329/bjp.v19i2.72930

Keywords:

RU.521; Vascular endothelial injury; Neutrophil extracellular traps, Western blot

Abstract

This study aims to investigate the effect of RU.521 on improving vascular endothelial injury in 14 acute lung injury patients. Serum myeloperoxidase, double-stranded DNA (dsDNA), IFN-β, and TNF-α levels of patients were detected by ELISA. Neutrophil extracellular traps were used to stimulate human venous endothelial cells (HUVEC). cGAS/STING pathway protein was detected by western blot. The protective effect of RU.521 on HUVEC was evaluated by CCK-8. The effects of RU.521 on cGAS/STING pathway expression were detected by PCR and western blot. The levels of myeloperoxidase and (dsDNA) in acute lung injury patients were significantly increased (p<0.05). The expression level of IFN-β in acute lung injury patients was significantly increased (p<0.05). The expression of cGAS and STING proteins in HUVEC cells was significantly increased (p<0.05), and the expression of IFN-β was significantly increased (p<0.05). RU.521 can ameliorate vascular endothelial injury. RU.521 inhibited cGAS/SRING mRNA and protein expression (p<0.05). Thus, neutrophil extracellular traps release dsDNA activates the cGAS/STING pathway-induced vascular endothelial injury in acute lung injury patients. RU.521 protects vascular endothelial injury by inhibiting the cGAS/STING pathway.

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References

Decout A, Katz JD, Venkatraman S, Ablasser A. The cGAS-STING pathway as a therapeutic target in inflammatory diseases. Nat Rev Immunol. 2021; 21: 548-69.

Fei Y, Huang X, Ning F, Qian T, Cui J, Wang X, Huang X. NETs induce ferroptosis of endothelial cells in LPS-ALI through SDC-1/HS and downstream pathways. Biomed Pharmacother. 2024; 175: 116621.

Han Y, Eom YS, Shah FH, Kim SJ. Destabilising microtubule polymerization regulates chondrocyte dedifferentiation and inflammation via nuclear factor kappa b and β-catenin pathway. Bangladesh J Pharmacol. 2023; 18: 8-16.

Li G, Liu S, Chen Y, Zhao J, Xu H, Weng J, Yu F, Xiong A, Udduttula A, Wang D, Liu P, Chen Y, Zeng H. An injectable liposome-anchored teriparatide incorporated gallic acid grafted gelatin hydrogel for osteoarthritis treatment. Nat Commun. 2023; 14: 3159.

Li J, Lu Y, Lin G. Blocking cGAS/STING signaling protects against sepsis-associated acute liver injury. Int Immunopharmacol. 2022; 113: 109276.

Li X, Wang Y, Chen Y, Lu Z, Sun Y, Zhong C, Lv Z, Pan H, Chen J, Yao D, Huang X, Yu C. Icariside II alleviates lipopolysaccharide-induced acute lung injury by inhibiting lung epithelial inflammatory and immune responses mediated by neutrophil extracellular traps. Life Sci. 2024; 346: 122648.

Lim HS, Jang Y, Moon BC, Park G. NF-κB signaling contribu-tes to the inhibitory effects of Bombyx batryticatus on neuroinflammation caused by MPTP toxicity. Bangladesh J Pharmacol. 2021; 16: 96-102.

Liu H, Yu X, Yu S, Kou J. Molecular mechanisms in lipopolysaccharide-induced pulmonary endothelial barrier dysfunction. Int Immunopharmacol. 2015; 29: 937-46.

Munshi L, Mancebo J, Brochard LJ. Noninvasive respiratory support for adults with acute respiratory failure. N Engl J Med. 2022; 387: 1688-98.

Qiao X, Yin J, Zheng Z, Li L, Feng X. Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: Pathogenesis and therapeutic implica-tions. Cell Commun Signal. 2024; 22: 241.

Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: The Berlin definition. JAMA. 2012; 307: 2526-33.

Raybuck AL, Lee K, Cho SH, Li J, Thomas JW, Boothby MR. mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes. FASEB J . 2019; 33: 13202-15.

Uthaman S, Parvinroo S, Mathew AP, Jia X, Hernandez B, Proctor A, Sajeevan KA, Nenninger A, Long MJ, Park IK, Chowdhury R, Phillips GJ, Wannemuehler MJ, Bardhan R. Inhibiting the cGAS-STING pathway in ulcerative colitis with programmable micelles. ACS Nano. 2024; 18: 12117-33.

Wei C, Huang Q, Zeng F, Ma L, Bai X, Zhu X, Gao H, Qi X. Cyclic guanosine monophosphate-adenosine monophosphate synthetase/stimulator of interferon genes signaling aggravated corneal allograft rejection through neutrophil extracellular traps . Am J Transplant. 2024: S1600-6135(24)00281-8.

Xie J, Zhu CL, Wan XJ, Zhao ZZ, Meng Y, Li P, Guo Y, Liu Q, Bian JJ, Deng XM, Wang JF. GSDMD-mediated NETosis promotes the development of acute respiratory distress syndrome. Eur J Immunol. 2023; 53: e2250011.

Xie J, Wang H, Kang Y, Zhou L, Liu Z, Qin B, Ma X, Cao X, Chen D, Lu W, Yao C, Yu K, Yao X, Shang H, Qiu H, Yang Y. Chinese Epidemiological Study of Sepsis (CHESS) study investigators. The epidemiology of sepsis in Chinese ICUs: A national cross-sectional survey. Crit Care Med. 2020; 48: e209-18.

Zhang Y, Li Z, Hong W, Hsu S, Wang B, Zeng Z, Du S. STING-dependent sensing of self-DNA driving pyroptosis contributes to radiation-induced lung injury. Int J Radiat Oncol Biol Phys. 2023; 117: 928-41.

Zhao J, Zhen N, Zhou Q, Lou J, Cui W, Zhang G, Tian B. NETs promote inflammatory injury by activating cGAS-STING pathway in acute lung injury. Int J Mol Sci. 2023; 24: 5125.

Zhu S, Yu Y, Qu M, Qiu Z, Zhang H, Miao C, Guo K. Neutrophil extracellular traps contribute to immuno-thrombosis formation via the STING pathway in sepsis-associated lung injury. Cell Death Discov. 2023; 9: 315.

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Published

2024-06-15

How to Cite

Zhang, B., Z. Fang, Y. . Lin, Q. Wu, and J. Chen. “RU.521 Protects Against Neutrophil Extracellular Traps-Induced Vascular Endothelial Injury by Inhibiting cGAS/STING Pathway”. Bangladesh Journal of Pharmacology, vol. 19, no. 2, June 2024, pp. 59-64, doi:10.3329/bjp.v19i2.72930.

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Section

Research Articles