共 34 条
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
来源:
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
相关论文