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Tanshinone IIA inhibits NLRP3 activation and attenuates alveolar macrophage pyroptosis via the TREM2/β-catenin pathway.
- Source :
-
Biocell . 2024, Vol. 48 Issue 10, p1475-1487. 13p. - Publication Year :
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MYELOID cells
*ADENOSINE triphosphate
*PYROPTOSIS
*PYRIN (Protein)
*CELL survival
Subjects
Details
- Language :
- English
- ISSN :
- 03279545
- Volume :
- 48
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Biocell
- Publication Type :
- Academic Journal
- Accession number :
- 180152135
- Full Text :
- https://doi.org/10.32604/biocell.2024.053227