Liu Limin, Wang Lianyun, Zhao Yangxing, Wang Yajing, Wang Zhaoxia, Qiao Zhongdong
School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuanlu, 200240 Shanghai, People's Republic of China.
Parasitol Res. 2006 Jul;99(2):189-93. doi: 10.1007/s00436-006-0168-1. Epub 2006 Mar 18.
Leishmania donovani (L. donovani) is an obligatory intracellular pathogen that resides and multiplies in the macrophages and has been found to alter the signaling parameters of the host. Testosterone plays a key role as signaling molecules in the regulation of parasite infections and could increase L. donovani infection of macrophages. The mitogen-activated protein kinases (MAPKs) pathway participates in the regulation of functions involved in parasite infection and host defense. In this work, the possibility that modulation of components of MAPK signaling may participate in the L. donovani infection was investigated. We found in this study that L. donovani infection upregulated p38 MAPK of bone marrow-derived macrophage, but not the other MAPK families, extracellular signal-related kinase 1 and 2, and c-jun N-terminal kinase (JNK), as evaluated by Western blotting with specific anti-MAPK antibodies. Moreover, we found that testosterone did not in itself interfere with the MAPKs but attenuated the L. donovani activation of p38 MAPK. The inhibition of p38 MAPK might be responsible for the testosterone-induced higher L. donovani infection since SB203580, a specific inhibitor of p38 MAPK, augmented L. donovani infection too. Collectively, our data indicated that the testosterone-enhanced L. donovani survival in macrophages might be due to the attenuation of MAPK signaling pathway by testosterone.
杜氏利什曼原虫（L. donovani）是一种专性细胞内病原体，寄生于巨噬细胞并在其中繁殖，且已发现它会改变宿主的信号参数。睾酮作为信号分子在寄生虫感染的调节中起关键作用，并且可能会增加巨噬细胞对杜氏利什曼原虫的感染。丝裂原活化蛋白激酶（MAPKs）通路参与调节与寄生虫感染和宿主防御相关的功能。在这项研究中，我们调查了MAPK信号通路成分的调节是否可能参与杜氏利什曼原虫感染。通过用特异性抗MAPK抗体进行蛋白质印迹分析，我们发现在本研究中，杜氏利什曼原虫感染上调了骨髓来源巨噬细胞的p38 MAPK，但未上调其他MAPK家族，即细胞外信号调节激酶1和2以及c-jun氨基末端激酶（JNK）。此外，我们发现睾酮本身并不干扰MAPKs，但会减弱杜氏利什曼原虫对p38 MAPK的激活。p38 MAPK的抑制可能是睾酮诱导杜氏利什曼原虫感染增加的原因，因为p38 MAPK的特异性抑制剂SB203580也会增强杜氏利什曼原虫的感染。总体而言，我们的数据表明，睾酮增强杜氏利什曼原虫在巨噬细胞中的存活可能是由于睾酮对MAPK信号通路的减弱作用。
