Proviral integration site 2 is required for interleukin-6 expression induced by interleukin-1, tumour necrosis factor-α and lipopolysaccharide

被引:12
作者
Yang, Jianfei [1 ]
Li, Xiang [1 ]
Hanidu, Adedayo [2 ]
Htut, Tin M. [1 ]
Sellati, Rosemarie [1 ]
Wang, Lian [3 ]
Jiang, Huiping [2 ]
Li, Jun [1 ]
机构
[1] Boehringer Ingelheim Pharmaceut Inc, Dept Immunol & Inflammat, Ridgefield, CT 06877 USA
[2] Boehringer Ingelheim Pharmaceut Inc, Dept Translat Sci, Ridgefield, CT 06877 USA
[3] Boehringer Ingelheim Pharmaceut Inc, Dept Cardiovasc Dis, Ridgefield, CT 06877 USA
关键词
cytokines; gene regulation; interleukin-6; kinase; provirus integratin site 2; PIM KINASES; TRANSGENIC MICE; CELL; IDENTIFICATION; GENES; GAMMA; ACTIVATION; LEUKEMIA; POTENT; BETA;
D O I
10.1111/j.1365-2567.2010.03286.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
P>PIM (proviral integration site) kinases are a distinct class of serine/threonine-specific kinases consisting of PIM1, PIM2 and PIM3. PIM2 is known to function in apoptosis pathways. Expression of PIM2 is highly induced by pro-inflammatory stimuli but the role of PIM2 in the expression of pro-inflammatory cytokines is unclear. In this study, we showed that over-expression of PIM2 in HeLa cells as well as in human umbilical vein endothelial cells enhanced interleukin-1 beta (IL-1 beta) -induced and tumour necrosis factor-alpha-induced IL-6 expression, whereas over-expression of a kinase-dead PIM2 mutant had the opposite effect. Studies with small interfering RNA specific to PIM2 further confirmed that IL-6 expression in HeLa cells requires PIM2. To investigate the function of PIM2 further, we generated PIM2-deficient mice. It was found that IL-6 production was significantly decreased from PIM2-deficient spleen cells after stimulation with lipopolysaccharide. Taken together, we demonstrated an important function of PIM2 in controlling the expression of the pro-inflammatory cytokine IL-6. PIM2 inhibitors may be beneficial for IL-6-mediated diseases such as rheumatoid arthritis.
引用
收藏
页码:174 / 182
页数:9
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