IL-21 regulates macrophage activation in human monocytic THP-1-derived macrophages

Abstract

Background: Interleukin-21 (IL-21) has a regulatory effect on various immune cells. Its effect on macrophage function remains unclear. Aims: This study aimed to investigate the effect of IL-21 on the macrophages-mediated inflammatory response and explore its mechanism. Materials & Methods: Phorbol myristate acetate was used to induce THP-1-derived macrophages. Then, cells were stimulated with IL-21 and/or lipopolysaccharide (LPS). To determine the effect of IL-21 on the production of inflammatory factors in THP-1-derived macrophages, the messenger RNA (mRNA) and protein levels of IL-6, tumor necrosis factor-α (TNF-α), IL-8, and IL-10 were detected by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Meanwhile, to explore the effect of IL-21 on macrophage polarization, macrophage phenotype, gene expression, and cytokine secretion mediated by THP-1-derived macrophage were detected by flow cytometry, RT-PCR, and ELISA. Results: First, we found that the IL-21 receptor was expressed in THP-1-derived macrophages. IL-21 enhanced LPS-mediated TNF-α, IL-6, and IL-10 production in THP-1-derived macrophages. During the polarization of THP-1-derived macrophages to M1-like macrophages, IL-21 induced the expression of macrophage surface markers CD86 and CD80, and related genes, such as TNF-α, IL-6, IL-1β, and DC-SIGN mRNA, inhibited Dectin-1 mRNA expression and promoted the secretion of TNF-α. During the polarization of THP-1-derived macrophages to M2-like macrophages, IL-21 enhanced the expression of macrophage surface markers CD86 and CD163, and related genes, such as TNF-α, IL-1β, IL-10, Dectin-1, and DC-SIGN mRNA, and promoted the secretion of IL-10. Conclusion: IL-21 promotes LPS-mediated production of inflammatory cytokines by THP-1-derived macrophages; IL-21 plays a two-way regulatory role in THP-1-derived macrophage polarization.