Open Access

ARTICLE

Tanshinone IIA inhibits NLRP3 activation and attenuates alveolar macrophage pyroptosis via the TREM2/β-catenin pathway

MIN LIU^1,*, XIA LI², JUN LIU¹, YU LIU¹

1 Department of Respiratory, Hunan Provincia Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, China
2 Hunan Academy of Traditional Chinese Medicine, Changsha, 410006, China

* Corresponding Author: MIN LIU. Email:

(This article belongs to the Special Issue: Cell Death and Inflammation in Signaling and Diseases)

BIOCELL 2024, 48(10), 1475-1487. https://doi.org/10.32604/biocell.2024.053227

Received 28 April 2024; Accepted 28 August 2024; Issue published 02 October 2024

Abstract

Background: Alveolar macrophage pyroptosis exacerbates inflammatory lung diseases, and tanshinone IIA is known for its anti-inflammatory properties. Thus, understanding how tanshinone IIA affects alveolar macrophage pyroptosis is essential. Methods: NR8383 cells were exposed to lipopolysaccharide (LPS) and adenosine triphosphate (ATP). We assessed cell viability, pyroptosis, and the expression of triggering receptors expressed on myeloid cells 2 (TREM2), p-β-catenin, β-catenin, and pyroptosis-related factors. We also examined the interaction between tanshinone IIA and TREM2. Results: Co-stimulation with LPS and ATP significantly reduced NR8383 cell viability, increased pyroptosis, and upregulated pyroptosis-associated factors. Treatment with tanshinone IIA mitigated these effects. Tanshinone IIA was effectively bound to the TREM2 protein. Knockdown of TREM2 reduced its expression and the p-β-catenin and β-catenin levels, thereby reversing the protective effects of tanshinone IIA. Conversely, overexpression of TREM2 enhanced NR8383 cell viability, reduced pyroptosis, and suppressed pyroptosis-related factors following LPS and ATP co-stimulation. Furthermore, the NOD-like receptor family pyrin domain containing 3 (NLRP3) activation reversed the reduced pyroptosis induced by β-catenin overexpression. β-catenin knockdown reversed the protective effects of TREM2 overexpression, and activation of NLRP3 exacerbated pyroptosis in β-catenin knockdown cells. Conclusion: Tanshinone IIA inhibited NLRP3 activation and alleviated alveolar macrophage pyroptosis through the TREM2/β-catenin pathway.

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Keywords

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