Characterization of stanniocalcin-1 expression in macrophage differentiation

Human stanniocalcin-1 (STC1) is a paracrine factor associated with inflammation and carcinogenesis. The role of STC1 in the pro- and anti-inflammatory functions of differentiating macrophage, however, is not clear. In this study, our data showed that phorbol 12-myristate 13-acetate (PMA) treatment induced human leukemia monocytic cells (ThP-1) differentiation to M0 macrophages. The differentiation was accompanied by a significant increase in the mRNA expression levels of STC1, the pro-inflammatory cytokine TNFα, and anti-inflammatory markers, CD163 & CD206. An intermitted removal of PMA treatment reduced the mRNA levels of STC1 and TNFα but had no noticeable effects on the anti-inflammatory markers. The correlation in the expression of STC1 and pro-inflammatory markers in differentiating macrophages was investigated, using siRNA(STC1)-transfected PMA-induced cells. Consistently, the transcripts levels of TNFα and IL-6 were significantly reduced. Moreover, LPS/IFNγ-induced M1-polarization showed remarkably higher expression levels of STC1 than IL-4/IL-13-induced M2-macrophages and PMA-induced M0-macrophages. Transcriptomic analysis of siRNA(STC1)-transfected M1-polarized cells revealed an upregulation of TBC1 domain family member 3 (TBC1D3G). The gene regulates the payload of macrophage-released extracellular vesicles to mediate inflammation. The conditioned media from siRNA(STC1)-transfected M1-polarized cells were found to reduce Hep3B cell motility. The data suggest that the expression of STC1 were associated with macrophage differentiation, but preferentially to M1 polarization.