Imatinib Inhibits the Inflammatory Phenotype of Macrophage Induced by Lipopolysaccharide / 中山大学学报(医学科学版)

ABSTRACT

@#【Objective】To investigate the effect of Imatinib（Ima）on the inflammatory phenotype of RAW264.7 mac⁃ rophages induced by lipopolysaccharide（LPS）.【Methods】RAW264.7 cells were treated by LPS（0.1 μg/mL）and/or Ima（1 μmol/L，5 μmol/L）. The mRNA levels of IL-1β，IL-10，CCL2，iNOS，TNF-α and Arg1 in RAW264.7 cells were tested by Q-PCR. The iNOS protein level and the activation of NF-κB and MAPK signal pathways were detected by Western Blot. The protein levels of IL-1β，CCL2，IL-10 and TNF-α in cell supernatant were detected by ELISA. 【Results】Compared with the normal control group，the mRNA levels of IL-1β，CCL2，iNOS，TNF-α and IL-10 were significantly increased in RAW264.7 cells treated with LPS for 8 h（P < 0.001）. In addition，the cell supernatant protein levels of IL-1β，IL-10，CCL2 as well as TNFα and the iNOS protein level were significantly increased in RAW264.7 cells stimulated by LPS for 24 h（P < 0.001）. Moreover，the phosphorylation levels of p65，p38，ERK and AKT were enhanced in RAW264.7 cells after treatment with LPS for 24 h. Compared with LPS group，pretreatment with Ima decreased the mRNA and protein levels of IL-1β，CCL2，iNOS and TNF-α（P < 0.01，P < 0.001），but increased the mRNA and protein level of IL-10（P < 0.001）. And this effect of Ima was dose-dependent. The phosphorylation levels of p65，p38， ERK and AKT were decreased in LPS+Ima group compared with that in LPS group. The functional status of RAW264.7 cells did not change significantly after treatment with Ima alone.【Conclusions】The effect of Imatinib to inhibit the inflammato⁃ ry phenotype of macrophage is related to retarding the overactivation of NF-κB and MAPK signaling pathways.