Exosomal HMGB3 released by glioma cells confers the activation of NLRP3 inflammasome and pyroptosis in tumor-associated macrophages.

Autor: Hu P; Department of Neurosurgery, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province 330006, PR China., Yan T; Department of Neurosurgery, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province 330006, PR China., Lv S; Department of Neurosurgery, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province 330006, PR China., Ye M; Department of Neurosurgery, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province 330006, PR China., Wu M; Department of Neurosurgery, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province 330006, PR China., Fang H; Department of Neurosurgery, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province 330006, PR China., Xiao B; Department of Neurosurgery, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province 330006, PR China. Electronic address: xiaobing9016@163.com.
Jazyk: angličtina
Zdroj: Tissue & cell [Tissue Cell] 2024 Jun; Vol. 88, pp. 102406. Date of Electronic Publication: 2024 May 12.
DOI: 10.1016/j.tice.2024.102406
Abstrakt: Background: Previous evidences has highlighted the pivotal role of NOD-like receptor family pyrin domain-containing 3 (NLRP3)-mediated inflammasomes and pyroptosis activation in driving tumor malignancy and shaping the tumor microenvironment. Herein, we aimed to elucidate the impact of high-mobility group box 3 (HMGB3) released in glioma-derived exosomes on macrophage infiltration in gliomas, NLRP3 inflammasome activation and polarization.
Methods: Transcripts and protein levels of HMGB3, and cytokines associated with macrophage phenotypes and pyroptosis were assessed in glioma tissues and cell lines (U251, LN229, T98G, A172) using qRT-PCR and/or Western blot analysis. Exosomes secreted from LN229 and NHA cells were isolated via differential ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and analysis of exosome-related markers. PKH67 staining was employed to examine exosomes uptake by THP-1 differentiated macrophages. Flow cytometry was utilized to assess macrophage pyroptotic rates and polarization-related markers.
Results: HMGB3 expression was elevated in glioma tissues, serum samples and tumor cell lines. Kaplan-Meier curves revealed a positive correlation between higher HMGB3 expression and poor overall survival and recurrence-free survival. Moreover, glioma tissues with increased HMGB3 expression exhibited significant upregulation of M2 macrophages markers (CD68, CD206, Arg1) and NLRP3 inflammasome components (NLRP3, IL-1β, ASC), suggesting that HMGB3 was closely associated with macrophage infiltration and NLRP3 inflammasome activation. Notably, HMGB3 was found to be enriched in glioma cell- secreted exosomes and could be internalized by macrophages. Knockdown of HMGB3 in glioma cell exosomes could restrain M2 macrophage polarization, NLRP3 inflammasome activation and pyroptosis.
Conclusion: These findings suggested that glioma cells secreted exosomal HMGB3 could facilitate macrophage M2 polarization, pyroptosis and inflammatory infiltration, indicating HMGB3 might be a poor prognosis factor for glioma.
Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: