Scholarlink

Background <p>Dendritic cells (DCs) regulate the equilibrium between immune activation and tolerance. Recent findings indicate that anthelmintic pyrvinium pamoate (PYR) has the potential to reprogram anti-inflammatory signaling pathways associated with myeloid cells. We examined whether PYR alters the phenotype and cytokine transcript profile of human monocyte-derived DCs (moDCs) by attenuating lipopolysaccharide (LPS)-driven inflammatory activation.</p> Methods <p>Ficoll density gradient was used to isolate peripheral blood mononuclear cells (PBMCs) from healthy donor. Plastic adherence was used to obtain monocytes, which were then differentiated into moDCs in RPMI supplemented with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). LPS was used to induce maturation. PYR was administered to parallel cultures prior to LPS. Using 18&#xa0;S as a reference, inflammatory/anti-inflammatory transcripts (IL-1β, IL-12, tumor necrosis factor (TNF)-α, IL-10, and indoleamine 2,3-dioxygenase (IDO)) were measured by qRT-PCR, and DC phenotype (CD11c, human leukocyte Ag (HLA)-DR, CD86, and CD14) was evaluated by flow cytometry.</p> Results <p>PYR-moDCs had significantly lower surface expression of CD86 (<i>P</i> ≤ 0.001***), CD11c (<i>P</i> ≤ 0.05*), and HLA-DR (<i>P</i> ≤ 0.0001****) than moDCs; PYR-moDCs also showed lower mRNA expression of <i>IL-12</i> (<i>P</i> ≤ 0.0001****), <i>IL-1β</i> (<i>P</i> ≤ 0.001***), and <i>TNF-α</i> (<i>P</i> ≤ 0.0001****) and higher <i>IL-10</i> mRNA expression (<i>P</i> ≤ 0.05*), while <i>IDO1</i> mRNA expression level was reduced (<i>P</i> ≤ 0.05*).</p> Conclusion <p>PYR affects the differentiation and maturation of human moDCs, resulting in an activation-attenuated, anti-inflammatory DC phenotype and gene expression pattern following LPS stimulation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Pyrvinium Pamoate Inhibits Differentiation and Maturation of Human Monocyte-derived Dendritic Cells and Shifts them Toward an Anti-inflammatory Phenotype

  • 期刊论文

  • 发表日期：

    2026年3月21日

查看全文
  • Shiva Alipour,
  • Sepideh Sohrabi,
  • Zahra Ghahramanipour,
  • Amirhossein Mardi,
  • Elham Mehdizadehfar,
  • Behzad Baradaran

摘要

Background

Dendritic cells (DCs) regulate the equilibrium between immune activation and tolerance. Recent findings indicate that anthelmintic pyrvinium pamoate (PYR) has the potential to reprogram anti-inflammatory signaling pathways associated with myeloid cells. We examined whether PYR alters the phenotype and cytokine transcript profile of human monocyte-derived DCs (moDCs) by attenuating lipopolysaccharide (LPS)-driven inflammatory activation.

Methods

Ficoll density gradient was used to isolate peripheral blood mononuclear cells (PBMCs) from healthy donor. Plastic adherence was used to obtain monocytes, which were then differentiated into moDCs in RPMI supplemented with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). LPS was used to induce maturation. PYR was administered to parallel cultures prior to LPS. Using 18 S as a reference, inflammatory/anti-inflammatory transcripts (IL-1β, IL-12, tumor necrosis factor (TNF)-α, IL-10, and indoleamine 2,3-dioxygenase (IDO)) were measured by qRT-PCR, and DC phenotype (CD11c, human leukocyte Ag (HLA)-DR, CD86, and CD14) was evaluated by flow cytometry.

Results

PYR-moDCs had significantly lower surface expression of CD86 (P ≤ 0.001***), CD11c (P ≤ 0.05*), and HLA-DR (P ≤ 0.0001****) than moDCs; PYR-moDCs also showed lower mRNA expression of IL-12 (P ≤ 0.0001****), IL-1β (P ≤ 0.001***), and TNF-α (P ≤ 0.0001****) and higher IL-10 mRNA expression (P ≤ 0.05*), while IDO1 mRNA expression level was reduced (P ≤ 0.05*).

Conclusion

PYR affects the differentiation and maturation of human moDCs, resulting in an activation-attenuated, anti-inflammatory DC phenotype and gene expression pattern following LPS stimulation.