Tzeh Gung Andrew Yeu, Kondo Hidehiro, Aoki Takashi, Hirono Ikuo
Laboratory of Genome Science, Tokyo University of Marine Science and Technology, Konan 4-5-7, Minato-Ku, 108-8477 Tokyo, Japan.
Fish Shellfish Immunol. 2009 Feb;26(2):230-4. doi: 10.1016/j.fsi.2008.11.006. Epub 2008 Nov 27.
The acute phase response, an important aspect of innate immunity, leads to the production of acute phase proteins (APPs) in the liver which would consequently help restore homeostasis to the body. Here, we identified a novel cytokine, growth differentiation factor 15 (GDF15) from Japanese flounder. Three out of the 384 EST sequences derived from liver of Japanese flounder treated with formalin-killed Edwardsiella tarda showed significant homology with GDF of various species. After obtaining the full-length cDNA, the deduced amino acid sequence exhibited low identity (<30%) with GDF15s of higher vertebrates. The predicted ORF of JFGDF15 revealed a signaling peptide at the N terminal, a TGFbeta propeptide domain and a TGFbeta domain. The mature peptide domain of JFGDF15 contains an RXXR motif, a furin cleavage site, required for the release of the mature peptide and conserved amino acids, which are signature features of TGFbeta superfamily proteins. JFGDF15 mRNA transcripts were detected in fish, 6h post-injection with PBS. The transcripts were highly up-regulated in liver at 6h post-injection with formalin-killed E. tarda. Moreover, up-regulation of the transcripts was also observed at 12h post-injection with formalin-killed Streptococcus iniae.
急性期反应是固有免疫的一个重要方面，可导致肝脏中急性期蛋白（APPs）的产生，从而有助于恢复机体的内环境稳态。在此，我们从日本牙鲆中鉴定出一种新型细胞因子——生长分化因子15（GDF15）。在用福尔马林灭活迟缓爱德华氏菌处理的日本牙鲆肝脏来源的384个EST序列中，有3个与各种物种的GDF显示出显著同源性。获得全长cDNA后，推导的氨基酸序列与高等脊椎动物的GDF15s具有较低的同一性（<30%）。JFGDF15的预测开放阅读框在N端显示一个信号肽、一个TGFβ前肽结构域和一个TGFβ结构域。JFGDF15的成熟肽结构域包含一个RXXR基序，这是一个弗林蛋白酶切割位点，是释放成熟肽所必需的，还有保守氨基酸，这些都是TGFβ超家族蛋白的标志性特征。在注射PBS 6小时后的鱼体内检测到JFGDF15 mRNA转录本。在用福尔马林灭活的迟缓爱德华氏菌注射后6小时，肝脏中的转录本高度上调。此外，在用福尔马林灭活的海豚链球菌注射后12小时也观察到转录本的上调。
