Abstract: Liu Caixia, Du Leilei, Duan Zhimin, Zeng Rong, Shen Yongnian, Hu Suquan, Liu Weida, Chen Qing, Li Min Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China （Liu CX, Du LL, Duan ZM, Zeng R, Shen YN, Hu SQ, Liu WD, Li M）; Research Laboratory, Jiangsu Province Blood Center, Nanjing 210042, China （Chen Q） Corresponding authors: Li Min, Email: drlimin@sina.cn; Chen Qing, Email: qngchen@hotmail.com 【Abstract】 Objective To evaluate effects of the yeast form of Sporothrix schenckii on activation of p38 mitogen-activated protein kinase （p38MAPK） and of interleukin-6 （IL-6） in macrophage-like THP-1 cells, which were differentiated from the human acute monocytic leukemia cell line THP-1. Methods THP-1 macrophage-like cells were divided into 3 groups to be treated with the yeast form of Sporothrix schenckii at a concentration of 2 × 106 colony-forming units （CFU）/ml （yeast form group）, 100 mg/L curdlan （curdlan group） and RPMI 1640 medium （blank control group） respectively. Real-time fluorescence-based quantitative PCR was performed to measure the mRNA of IL-6 in THP-1 macrophage-like cells in the above 3 groups after 3- and 6-hour treatment separately, and enzyme-linked immunosorbent assay （ELISA） to detect the level of IL-6 in the culture supernatant of THP-1 macrophage-like cells after 24-hour treatment. Western blot analysis was conducted to determine the protein of p38MAPK and phosphorylated p38MAPK （p-p38MAPK） in the above 3 groups after 30- and 60-minute treatment separately. Other THP-1 macrophage-like cells were pretreated with 100 nmol/L dexamethasone （a p38MAPK inhibitor） for 30 minutes, and then were divided into 3 groups to be treated with the yeast form of Sporothrix schenckii, curdlan and RPMI 1640 medium respectively, and changes in the level of p-p38MAPK and mRNA of IL-6 were also detected. Statistical analysis was carried out with SPSS19.0 software by using one-way or multi-way analysis of variance and least significant difference （LSD） test. Results Significant differences in the mRNA of IL-6 in THP-1 macrophage-like cells were observed among the yeast form group, curdlan group and blank control group （F = 5 552.22, P < 0.001） after 3- hour treatment （56.81 ± 7.36, 26.69 ± 1.22 and 0.97 ± 0.05, respectively） and 6-hour treatment （378.03 ± 16.67, 276.24 ± 39.13 and 1.02 ± 0.04, respectively）. Additionally, the yeast form group showed significantly higher mRNA of IL-6 after 6-hour treatment than that after 3-hour treatment （q = 16.74, P < 0.001）. After 24-hour treatment, the level of IL-6 in the culture supernatant of THP-1 macrophage-like cells also significantly differed among the yeast form group, curdlan group and blank control group （59.96 ± 18.16 pg/L, 91.01 ± 17.27 pg/L, 5.50 ± 2.30 pg/L, respectively; F = 26.62, P < 0.01）, and was significantly higher in the yeast form group than in the blank control group （P < 0.01）. After 30- and 60-minute treatment, the protein of p-p38MAPK was significantly higher in the yeast form group than in the blank control group （both P < 0.01）. Moreover, the mRNA of IL-6 （4.46 ± 1.03 vs. 493.52 ± 113.87, P < 0.001） and protein of p-p38MAPK （2.29 ± 0.37 vs. 4.55 ± 0.46, q = 10.81, P < 0.01） were both significantly lower in the yeast form group with dexamethasone pretreatment than in that without dexamethasone pretreatment. Conclusion In vitro treatment with the yeast form of Sporothrix schenckii can enhance the of IL-6 in human THP-1 macrophage-like cells by activating the p38MAPK signaling pathway.