2. Academic Validation
  3. STING mediates SU5416/hypoxia-induced pulmonary arterial hypertension in rats by regulating macrophage NLRP3 inflammasome activation

STING mediates SU5416/hypoxia-induced pulmonary arterial hypertension in rats by regulating macrophage NLRP3 inflammasome activation

  • Immunobiology. 2023 Feb 8;228(2):152345. doi: 10.1016/j.imbio.2023.152345.
Dan-Dan Wu 1,  Yan Deng 2,  Juan Liao 1,  Shan-Shan Xie 1,  Hui Meng 1,  Wei-Fang Lan 1
Affiliations

Affiliations

  • 1 Department of Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • 2 Department of Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, China. Electronic address: [email protected].
PMID: 36780836 DOI: 10.1016/j.imbio.2023.152345
Abstract

Background: The NLRP3 inflammasome in macrophages is known to promote infection-related vascular growth, and NLRP3 inflammasome activation interacts with PAH. STING is a crucial inflammatory reaction link that can increase the overexpression of NLRP3. However, the expression and effect of STING in PAH have not been elucidated. We examined the expression and articulation of STING in PAH and researched its hidden mechanism.

Methods: A SU5416 plus hypoxia (Su/Hy)-induced rat model of PAH was constructed to examine STING activation. Su/Hy induced PAH rats were given a prophylactic injection of STING the inhibitor C-176. After modeling, hemodynamic changes, right ventricular hypertrophy index, lung morphological features, inflammasome activation, and proinflammatory cytokine secretion levels were assessed. In addition, the STING agonist DMXAA or inhibitor C-176 was used to interfere with LPS-induced BMDMs, NLRP3 inflammasome activation and cytokine secretion were examined, and the effect on PASMCs was evaluated in a coculture system.

Results: STING expression increased significantly in the lung tissue of Su/Hy-treated PAH rats compared with normoxia-treated rats. Moreover, STING inhibitors can alleviate the Su/Hy-induced increase in pulmonary artery pressure and restrain the activation of the NLRP3 inflammasome and proinflammatory cytokines. In vitro experiments confirmed that STING affected the expression of the NLRP3 inflammasome and the secretion of inflammatory cytokines in BMDMs and promoted the proliferation of PASMCs in the coculture system.

Conclusion: Our study shows that STING is activated in Su/Hy-induced PAH and boosts the actuation of the macrophage NLRP3 inflammasome to advance the inflammatory response and vascular proliferation in rats with Su/Hy-induced pulmonary hypertension.

Keywords

Inflammation; NLRP3 inflammasome; Pulmonary arterial hypertension; Pulmonary vascular remodeling; STING.

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