Cuesta Alberto, Meseguer José, Esteban Maria Angeles
Fish Innate Immune System Group, Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain.
Mol Immunol. 2008 Apr;45(8):2333-42. doi: 10.1016/j.molimm.2007.11.007. Epub 2007 Dec 27.
Antimicrobial peptides (AMPs) are important mediators of the immune response against bacteria and hepcidin is a 20-25 residues member with known functions in iron regulation and the innate immune response. Most studies have focused on mammalian organisms but very little is known about other vertebrate groups including teleost fish. Thus, based on the sequence of an EST database, we have characterized hepcidin gene organization, gene expression, distribution and in vitro and in vivo regulation, as well as the biological activity of a synthetic peptide in the teleost fish gilthead seabream (Sparus aurata L.). First, it was found that the seabream hep gene genomic organization is formed by 3 exons and 2 introns, while the mRNA transcript is constitutively detected in most of the fish tissues but mainly in peritoneal leucocytes, head-kidney, liver and skin. Moreover, we have identified for the first time that hep is much more highly expressed in acidophilic granulocytes than in monocyte-macrophages and lymphocytes. In vitro, hep expression is up-regulated by several mitogens, pathogen-associated molecular patterns (PAMPs) and particulated antigens. Not surprisingly, intraperitoneal injection of bacteria or virus led to a significant gene up-regulation in the liver, head-kidney, peritoneal exudate or spleen. These observations suggest a major role for seabream hepcidin in the immune response to bacteria and viruses. Furthermore, the synthetic seabream Hep exerted an important antimicrobial activity against several bacterial strains in vitro reducing their viability. To conclude, seabream hep gene expression, up-regulation after in vitro or in vivo treatment with mitogens, PAMPs or particulated antigens and the direct in vitro biological activity against bacteria demonstrate that it is an important antimicrobial peptide and probably plays an important role in the innate immune response of fish.
抗菌肽（AMPs）是抵抗细菌的免疫反应的重要介质，而铁调素是一种由20 - 25个氨基酸残基组成的成员，在铁调节和先天免疫反应中具有已知功能。大多数研究集中在哺乳动物身上，但对于包括硬骨鱼在内的其他脊椎动物群体知之甚少。因此，基于一个EST数据库的序列，我们已经对硬骨鱼金头鲷（Sparus aurata L.）的铁调素基因结构、基因表达、分布以及体外和体内调节，以及一种合成肽的生物学活性进行了表征。首先，发现金头鲷hep基因的基因组结构由3个外显子和2个内含子组成，而mRNA转录本在大多数鱼组织中都能组成性检测到，但主要在腹膜白细胞、头肾、肝脏和皮肤中。此外，我们首次发现hep在嗜酸性粒细胞中的表达比在单核细胞 - 巨噬细胞和淋巴细胞中高得多。在体外，hep的表达受到几种有丝分裂原、病原体相关分子模式（PAMPs）和颗粒性抗原的上调。不出所料，腹腔注射细菌或病毒会导致肝脏、头肾、腹膜渗出液或脾脏中的基因显著上调。这些观察结果表明金头鲷铁调素在对细菌和病毒的免疫反应中起主要作用。此外，合成的金头鲷铁调素在体外对几种细菌菌株具有重要的抗菌活性，降低了它们的活力。总之，金头鲷hep基因的表达、在体外或体内用有丝分裂原、PAMPs或颗粒性抗原处理后的上调以及对细菌的直接体外生物学活性表明它是一种重要的抗菌肽，可能在鱼类的先天免疫反应中起重要作用。
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