2. Academic Validation
  3. Artesunate attenuates serum amyloid A-induced M1 macrophage differentiation through the promotion of PHGDH

Artesunate attenuates serum amyloid A-induced M1 macrophage differentiation through the promotion of PHGDH

  • Int Immunopharmacol. 2023 Dec 29:127:111462. doi: 10.1016/j.intimp.2023.111462.
Xinhui Lu 1,  Yan Huang 2,  Mingqian Zhou 1,  Yixuan Guo 1,  Yihan Zhou 1,  Rongyun Wang 1,  Wumeng Jin 1,  Chengping Wen 1,  Yun Zhang 3,  Yujun Tang 4
Affiliations

Affiliations

  • 1 Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
  • 2 Zhejiang Cancer Hospital, Hangzhou Institution of Medicine (HIM), Chinese Academy of Science, Hangzhou, Zhejiang 310022, China.
  • 3 Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China. Electronic address: [email protected].
  • 4 Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China. Electronic address: [email protected].
PMID: 38159553 DOI: 10.1016/j.intimp.2023.111462
Abstract

Clinical studies indicated that Serum Amyloid A (SAA) might be a promising biomarker for forecasting the activity, severity, and adverse prognosis of systemic lupus erythematosus (SLE). Simultaneously, a positive correlation has been observed between macrophages, Th17 cells, and SLE disease activity, with both these immune cells being affected by SAA. Presently, the relationship between SAA and the aforementioned immune cell types in SLE remains to be elucidated. To discern the immune cell type most closely associated with SAA, we undertook a single-cell RNA sequencing data analysis via the GEO database. Subsequent results revealed a strong association between macrophages and SAA, a relationship further validated through flow cytometry of spleen macrophages in the MRL/lpr model. We discovered that SAA stimulate M1 macrophage differentiation along with the upregulation of pro-inflammatory cytokines such as IL-6 and IL-1β. Our findings suggest that SAA may promote M1 macrophage differentiation via the downregulation of phosphoglycerate dehydrogenase (PHGDH). Artesunate (ART), primarily utilized for malaria treatment, was shown to inhibit M1 macrophage differentiation and pro-inflammatory cytokine levels via upregulating the PHGDH expression, thereby attenuating the disease activity in SLE.

Keywords

Artesunate; Macrophages; PHGDH; Serum amyloid A; Systemic lupus erythematosus.

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