IL-12 p40 homodimer, but not IL-12 p70, induces the expression of IL-16 in microglia and macrophages.
IL-12 p40 homodimer, but not IL-12 p70, induces the expression of IL-16 in microglia and macrophages.
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DOI：
10.1016/j.molimm.2008.10.033
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发表时间：
2009-02
影响因子：
3.6
通讯作者：
Pahan K
中科院分区：
文献类型：
--
作者：
Jana M;Pahan K
IL-16是一种白细胞趋化因子，参与了多发性硬化症和其他自身免疫性疾病的发病过程。然而，这种LCF的表达机制还知之甚少。本研究强调了IL-12 p40同源二聚体(P402)在诱导原代小鼠和人小胶质细胞、小鼠BV-2小胶质细胞、小鼠腹膜巨噬细胞和RAW264.7细胞表达IL-16方面的重要性。相反，具有生物活性的异二聚体细胞因子IL-12p70不能诱导上述任何一种细胞表达IL-16。同样，IL-12p402也可诱导小胶质细胞中IL-16启动子的激活。在各种刺激中，p402对小胶质细胞IL-16启动子的激活作用最强，其次是p40单体、IL-16和IL-23。此外，p40而不是p35的过度表达和p402对IL-12p35(−/−)小鼠小胶质细胞IL-16的诱导表达证实了p40而不是p35是诱导IL-16的原因。最后，利用从IL-12Rβ1(−/−)和IL-12Rβ2(−/−)小鼠分离的原代小胶质细胞，我们证明了p402通过IL-12Rβ1而不是IL-12Rβ2诱导LCFs的表达。这些结果揭示了p402的一种新的生物学功能，并提出了IL-12 p402的生物学功能可能不同于IL-12 p70的可能性。
IL-16, a leukocyte chemoattractant factor (LCF), is involved in the disease process of multiple sclerosis and other autoimmune disorders. However, mechanisms by which this LCF is expressed are poorly understood. The present study underlines the importance of IL-12 p40 homodimer (p402), the so-called biologically inactive molecule, in inducing the expression of IL-16 in primary mouse and human microglia, mouse BV-2 microglial cells, mouse peritoneal macrophages, and RAW264.7 cells. In contrast, IL-12 p70, the bioactive heterodimeric cytokine, was unable to induce the expression of IL-16 in any of these cell types. Similarly IL-12 p402 also induced the activation of IL-16 promoter in microglia. Among various stimuli tested, p402 was the most potent one followed by p40 monomer, IL-16 and IL-23 in inducing the activation of IL-16 promoter in microglial cells. Furthermore, induction of IL-16 mRNA expression by over-expression of p40, but not p35, cDNA and induction of IL-16 expression by p402 in microglia isolated from IL-12p35 (−/−) mice confirm that p40, but not p35, is responsible for the induction of IL-16. Finally, by using primary microglia isolated from IL-12Rβ1 (−/−) and IL-12Rβ2 (−/−) mice, we demonstrate that p402 induces the expression of this LCF via IL-12Rβ1 but not IL-12Rβ2. These results delineate a novel biological function of p402 and raise the possibility that biological function of IL-12 p402 maybe different from IL-12 p70.
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影响因子：
4.8
作者：
Jana, M;Liu, XJ;Pahan, K
通讯作者：
Pahan, K
影响因子：
4.4
作者：
Jana, Malabendu;Jana, Arundhati;Pahan, Kalipada
通讯作者：
Pahan, Kalipada
影响因子：
4.4
作者：
Jana, Malabendu;Jana, Arundhati;Pahan, Kalipada
通讯作者：
Pahan, Kalipada
影响因子：
12.7
作者：
Engel, S;Schluesener, H;Meyermann, R
通讯作者：
Meyermann, R
DOI：
10.1084/jem.20052545
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Khader SA;Partida-Sanchez S;Bell G;Jelley-Gibbs DM;Swain S;Pearl JE;Ghilardi N;Desauvage FJ;Lund FE;Cooper AM
通讯作者：
Cooper AM