p38 MAPK plays a role in IL‐4 synthesis in jacalin plus CD28‐stimulated CD4+ T cells—II
p38 MAPK plays a role in IL‐4 synthesis in jacalin plus CD28‐stimulated CD4+ T cells—II
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DOI：
10.1189/jlb.0905513
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发表时间：
2006-06
影响因子：
5.5
通讯作者：
S. Tamma;Kun Wook Chung;Tejal Patel;S. Balan;S. Pahwa
中科院分区：
文献类型：
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作者：
S. Tamma;Kun Wook Chung;Tejal Patel;S. Balan;S. Pahwa
我们之前已经证明，雅加林是一种CD4+T细胞凝集素，可以诱导细胞内事件的磷酸化，中等水平的白细胞介素2的分泌。我们还发现，在CD28共刺激存在的情况下，JAX能诱导IL-4的分泌。在本研究中，我们发现在p38丝裂原活化蛋白激酶(MAPK)抑制剂SB203580存在的情况下，用雅加林+CD28交联剂(CD28XL)刺激正常的CD4+T细胞，可导致信号转导和转录激活因子(STAT)-6的磷酸化，以及Bcl一2和Bclxl的表达，而在p38丝裂原活化蛋白激酶(MAPK)抑制剂SB203580的存在下，这些信号转导和转录激活因子(STAT)-6的表达被显著地抑制。我们进一步产生了雅加林诱导的CD4+T细胞母细胞，检测了CD28XL的作用，并观察到p38的上调以及STAT-6、Bcl2和Bclxl的激活。在记忆性T细胞中，单用CD28可显著诱导p38MAPK和IL-4分泌的磷酸化，而在幼稚T细胞中，则需要JAX和CD28XL来诱导这些分子的产生。在CD28XL之前用p38抑制剂孵育细胞，导致所有这些分子的下调。进一步的IL-4治疗并没有扭转这一趋势。我们的研究表明，p38MAPK可能在这些分子的诱导中发挥重要作用，并可能在保护细胞免受凋亡的影响中发挥作用。
We have previously shown that jacalin, a CD4+ T cell lectin, induces phosphorylation of intracellular events, moderate levels of interleukin (IL)‐2 secretion. We have also shown that in the presence of CD28 costimulation, jacalin induces IL‐4 secretion. In the present study, we showed that stimulation of normal CD4+ T cells with jacalin plus CD28 cross‐linking (CD28XL) resulted in phosphorylation of signal transducer and activator of transcription (STAT)‐6 and expression of Bcl‐2 and Bcl‐xL, which were inhibited significantly when cells were cultured in the presence of the p38 mitogen‐activated protein kinase (MAPK) inhibitor SB203580. We further generated jacalin‐induced CD4+ T cell blasts, examined the effects of CD28XL, and observed enhanced up‐regulation of p38 and activation of STAT‐6, Bcl‐2, and Bcl‐xL. Engagement of CD28 alone induced a marked degree of phosphorylation of p38 MAPK and IL‐4 secretion in memory T cells (jacalin blasts), whereas in naïve T cells, jacalin plus CD28XL was required to induce these molecules. Incubation of cells with p38 inhibitor prior to CD28XL resulted in down‐modulation of all these molecules. Further treatment with IL‐4 has not reversed this trend. Our studies imply that p38 MAPK may play an important role in induction of these molecules and a putative role in protecting cells from undergoing apoptosis.