IL-1β alleviates suppressive potential of bone marrow mesenchymal stem cells in macrophage M1 polarization via autophagy mediated degradation of SPP1

  • Sci Rep. 2026 May 20. doi: 10.1038/s41598-026-52854-4.
Peng Ye  #  1 ,  Rui Bai  #  2 ,  Xiaoli Ding  #  2 ,  Pengcheng Gao  2 ,  Zheng Wang  2 ,  Na Wang  2 ,  Xi Zhu  2 ,  Hongbo Chen  2 ,  Long Wu  2 ,  Zhenyu Bai  2 ,  Rui Ma  3 ,  Zhidong Lu  4
Affiliations
  • 1. Department of Orthopedic, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750000, China. [email protected].
  • 2. Department of Orthopedic, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750000, China.
  • 3. Department of Obstetrics and Gynecology, Peking University First Hospital Ningxia Women and Children's Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan, Ningxia, 750000, China.
  • 4. Department of Orthopedic, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750000, China. [email protected].
  • # Contributed equally.
PMID: 42156848 DOI: 10.1038/s41598-026-52854-4
Abstract

The immunomodulatory properties of mesenchymal stem cells (MSCs) are often influenced by inflammatory microenvironment. However, the specific effects of IL-1β on immunomodulatory role of bone marrow derived MSCs (BMSCs) remain need to be understood. In this study, the role of Autophagy induced by IL-1β contributes to immunoregulatory effect of BMSCs on macrophage polarization was investigated. We isolated and characterized BMSCs through morphological analysis, flow cytometry, and differentiation potential. Interleukin 1β (IL-1β) was employed to stimulate BMSCs in vitro. Secreted phosphoprotein 1 (SPP1) expression, Autophagy and MAPK signaling in BMSC were examined by qRT-PCR, ELISA, Western blotting and confocal microscopy. Co-immunoprecipitation (Co-IP) assays were performed to evaluate the interaction between p62 and SPP1. The immunomodulatory function of BMSCs on macrophage polarization was identified by transwell co-culture system with macrophage cells THP-1. The macrophage-associated marker expression was analyzed using WB and immunofluorescence, while the secretion of inflammatory cytokines was measured by ELISA. Phenotypic characterization demonstrated that BMSCs possessed canonical MSC morphology, belong to CD73+CD90+CD105+/CD14-CD34-CD45-HLADR- cells, and differentiated into adipogenic, osteogenic, and chondrogenic lineages. Co-culture of BMSCs with THP-1 inhibits M1 polarization, which was alleviated by IL-1β treatment. IL-1β had capability to induce Autophagy by which increasing SPP1 degradation via p62 interaction. Inhibiting Autophagy using Atg5 shRNA and recombinant SPP1 enhance immunomodulatory potential, while an SPP1-neutralizing antibody abolished this effect. Mechanistically, ERK1/2 phosphorylation mediated the regulation of Autophagy and SPP1 expression in IL-1β-treated BMSCs. In conclusion, our finding demonstrated that IL-1β impairs the immunomodulatory function of BMSCs on M1 macrophage polarization by ERK1/2 signaling mediated Autophagy related SPP1 degradation. Targeting Autophagy inhibition emerges as a promising strategy to enhance therapeutic potential of BMSCs.

Keywords
Autophagy; ERK1/2; IL-1β; Macrophage polarization; Secreted phosphoprotein 1; bone marrow mesenchymal stem cells.
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