Ulinastatin reduces LPS-induced THP-1 macrophage M1-like characteristics

作者：Yang, Zhouxin; Yan, Molei; Hu, Caibao; He, Shendi; Mao, Genxiang; Wang, Sanying; Feng, Yue; Cai, Guolong^*; Yan, Jing^*

来源：International Journal of Clinical and Experimental Medicine, 2018, 11(5): 4736-4741.

• Lipopolysaccharide
• macrophage polarization
• ulinastatin

Objective: Ulinastatin could inhibit inflammatory responses, and might be used for treating sepsis. Macrophages can be polarized to type 1 macrophages (M1) when stimulated by lipopolysaccharide and proinflammatory cytokines. M1 participates in proinflammatory responses and is vital in host defense against bacterial and viral infections. However, the regulation of macrophage polarization by ulinastatin is not clear yet. Methods: Ulinastatin (2000 U/mL) was used to treat lipopolysaccharide (LPS) (100 mu g/mL)-induced THP-1 macrophages. Proinflammatory cytokines were tested by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Cell surface markers were detected by flow cytometry. Total and phosphorylated p65, STAT (signal transducers and activators of transcription) 1, and STAT3 were detected by Western blotting. Results: Ulinastatin downregulated the secretion of proinflammatory cytokines interleukin (IL)-1 beta, tumor necrosis factor alpha, IL-6, and IL-12 by LPS-induced THP-1 macrophages (P < 0.01). The mRNA expression of these cytokines was also significantly reduced by ulinastatin. Ulinastatin also upregulated HLA-DR (human leukoyte Antigen DR) but downregulated CD163. The phosphorylation of p65, STAT1, and STAT3 in THP-1 macrophages decreased after ulinastatin treatment. Conclusion: Ulinastatin reduced THP1 macrophage M1-like characteristics after LPS treatment, suggesting that the therapeutic effect of ulinastatin on various diseases might be due to the regulation of macrophage polarization.

• 出版日期2018
• 单位浙江医院