Kiguchi Norikazu, Maeda Takehiko, Kobayashi Yuka, Fukazawa Yohji, Kishioka Shiroh
Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama 641-0012, Japan.
Biochem Biophys Res Commun. 2009 Jul 3;384(3):311-5. doi: 10.1016/j.bbrc.2009.04.121. Epub 2009 May 3.
Despite accumulating evidence, the role of leptin in chemokine expression is poorly understood. In this study, we evaluated the effects of leptin on CC-chemokine ligands (CCLs), CCL3, CCL4, and CCL5 gene expression in cultured murine macrophage, J774A.1 cells. Expression of all these CCLs mRNA was gradually increased and significant up-regulation was observed for 3-12 h exposure to leptin (1 microM). The phosphorylated signal transducer and activator of transcription 3 (pSTAT3) was significantly increased for 5-20 min exposure to leptin, and it was localized in leptin receptor-positive macrophage. Pretreatment with AG490 (100 microM), a janus kinase 2 (JAK2) inhibitor, significantly suppressed leptin-induced pSTAT3 increases and the up-regulation of CCLs mRNA expression. In conclusion, leptin enhances CCLs expression in cultured murine macrophage, through activation of a JAK2-STAT3 pathway. Therefore, a new paradigm of leptin-mediated chemokine expression may lead to the clarification of complex immune systems in future.
尽管有越来越多的证据，但瘦素在趋化因子表达中的作用仍知之甚少。在本研究中，我们评估了瘦素对培养的小鼠巨噬细胞J774A.1细胞中CC趋化因子配体（CCLs）、CCL3、CCL4和CCL5基因表达的影响。所有这些CCLs mRNA的表达均逐渐增加，并且在暴露于瘦素（1 microM）3至12小时后观察到显著上调。暴露于瘦素5至20分钟后，磷酸化信号转导子和转录激活子3（pSTAT3）显著增加，并且它定位于瘦素受体阳性巨噬细胞中。用酪氨酸激酶2（JAK2）抑制剂AG490（100 microM）预处理可显著抑制瘦素诱导的pSTAT3增加以及CCLs mRNA表达的上调。总之，瘦素通过激活JAK2-STAT3途径增强培养的小鼠巨噬细胞中CCLs的表达。因此，瘦素介导的趋化因子表达的新范例可能会在未来导致对复杂免疫系统的阐明。
