Elevated levels of cyclooxygenase-2 in antigen-stimulated mast cells is associated with minimal activation of p38 mitogen-activated protein kinase
Elevated levels of cyclooxygenase-2 in antigen-stimulated mast cells is associated with minimal activation of p38 mitogen-activated protein kinase
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DOI：
10.4049/jimmunol.167.3.1629
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发表时间：
2001-08-01
影响因子：
4.4
通讯作者：
Beaven, MA
中科院分区：
文献类型：
--
作者：
Hundley, TR;Prasad, AR;Beaven, MA
我们研究了肥大细胞在长期暴露于银后，类二十烷的产生发生变化的可能因素。银杏叶提取物(AG)刺激培养的RBL-2H3肥大细胞后，环氧合酶(COX-2)蛋白和消息的表达增加。没有诱导其他二十烷类化合物相关的酶，即COX-1，5-脂氧合酶和胞浆磷脂酶A(2)。在RBL-2H3细胞中，细胞外信号调节激酶、e-jun氨基末端激酶和p38丝裂原活化蛋白(MAP)激酶在COX-2诱导之前被激活，而磷脂酰肌醇3‘激酶及其底物Akt被结构性激活。对药物抑制剂的研究表明，在这些激酶中，只有p38MAPK调节COX-2的表达。P38 MAPK抑制剂SB202190可阻断COX-2的诱导，即使在Ag刺激后12~16h加入时，p38 MAPK活性已恢复到接近基础水平，但仍略有升高。有趣的是，SB202190显著降低未刺激细胞中COX-2、胞浆磷脂酶A(2)和5-脂氧合酶的表达。总之，这些结果表明，p38 MAP激酶在RBL-2H3细胞中以很低的活性水平被动或主动地调节二十烷类相关酶的表达。此外，与已发表的数据比较表明，不同的MAP激酶调节不同表型甚至相似表型的炎性细胞中COX-2的诱导，并提示在将结果从一种类型的细胞外推到另一种类型的细胞时要谨慎。
We have investigated possible factors that underlie changes in the production of eicosanoids after prolonged exposure of mast cells to Ag. Ag stimulation of cultured RBL-2H3 mast cells resulted in increased expression of cyclooxygenase (COX-2) protein and message. Other eicosanoid-related enzymes, namely COX-1, 5-lipoxygenase, and cytosolic phospholipase A(2) were not induced. Activation of extracellular signal-regulated kinase, e-Jun N-terminal kinase, and p38 mitogen-activated protein (MAP) kinase preceded the induction of COX-2, whereas phosphatidylinositol 3' kinase and its substrate, Akt, were constitutively activated in RBL-2H3 cells. Studies with pharmacologic inhibitors indicated that of these kinases, only p38 MAP kinase regulated expression of COX-2. The induction of COX-2 was blocked by the p38 MAP kinase inhibitor SB202190, even when added 12-16 h after stimulation with Ag when p38 MAP kinase activity had returned to near basal, but still minimally elevated, levels. Interestingly, expression of COX-2 as well as cytosolic phospholipase A(2) and 5-lipoxygenase were markedly reduced by SB202190 in unstimulated cells. Collectively, the results imply that p38 MAP kinase regulates expression of eicosanoid-related enzymes, passively or actively, at very low levels of activity in RBL-2H3 cells. Also, comparison with published data suggest that different MAP kinases regulate induction of COX-2 in inflammatory cells of different and even similar phenotype and suggest caution in extrapolating results from one type of cell to another.