Analysis of the novel mouse WAP motif proteins ELM1 and ELM2 and their human homologs

新型小鼠 WAP 基序蛋白 ELM1 和 ELM2 及其人类同源物的分析

• 批准号: 14370194
• 负责人: HAGIWARA Koichi
• 金额: $ 8.77万
• 依托单位: Saitama Medical School (2003)Tohoku University (2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370194/
• 关键词: SWAM1; SWAM2; WAP; SLPI; elafin; antibacterial protein; innate immunity; chromosome 20; ヒト染色体20番; マウス染色体2番; WAP遺伝子クラスター; ヒト相同遺伝子

Antibacterial proteins are important participants in the innate immunity system. Elafin and SLPI are the WAP motif proteins with both antibacterial activity and antiprotease activity, and their role in innate immunity is under intense investigation. We cloned two novel antibacterial WAP motif proteins from mice, SWAM1 and SWAM2. SWAM1 and SWAM2 are composed of a signal sequence and a single WAP motif that has high homologies with that of elafin and SLPI. SWAM1 is constitutively expressed in kidney, and epididymis, and is induced in the pneumonic lung. SWAM2 is constitutively expressed in tongue. SWAM1 and SWAM2 inhibit the growth of both Escherichia coli and Staphylococcus aureus at an 1C90 of 10 υM. Human genes LOC149709 and huWAP2 are considered to be human SWAM1 and SWAM2, respectively. These and several VAP motif proteins (WAP1, elafin, SLPI, HE4, eppin, C20orf170, LOC164237, and WFDC3) form a gene cluster on human chromosome 20, suggesting that they may be derived from the same ancestral gene by gene duplication. Our results underscore the role of the WAP motif as a skeletal motif to form antibacterial proteins, and warrant the study of antibacterial activity in other WAP motif proteins.

抗菌蛋白是先天免疫系统的重要参与者，Elafin 和 SLPI 是具有抗菌活性和抗蛋白酶活性的 WAP 基序蛋白，我们从小鼠身上克隆了两种新型抗菌 WAP 基序蛋白 SWAM1。 SWAM1和SWAM2由信号序列和单个WAP基序组成，与elafin和SLPI具有高度同源性。 SWAM1 在肾脏和附睾中持续表达，并在肺中被诱导。 SWAM1 和 SWAM2 在 1C90 为 10 υM 时抑制大肠杆菌和金黄色葡萄球菌的生长。分别被认为是人类 SWAM1 和 SWAM2。一些VAP基序蛋白（WAP1、elafin、SLPI、HE4、eppin、C20orf170、LOC164237和WFDC3）在人类20号染色体上形成一个基因簇，这表明它们可能通过基因复制源自相同的祖先基因。 WAP 基序作为形成抗菌蛋白的骨架基序的作用，并保证了抗菌活性的研究其他 WAP 基序蛋白。

项目成果

Kikuchi T., Hagiwara K., Honda Y, Gomi K., Kobayashi T., Takahashi H., Tokue Y., Watanabe A., Nukiwa T.: "Clarithromycin suppresses lipopolysaceharide-induced interleukin-8 production by human monocytes through AP-1 and NF-kB transcription factors."Journa

Kikuchi T.、Hagiwara K.、Honda Y、Gomi K.、Kobayashi T.、Takahashi H.、Tokue Y.、Watanabe A.、Nukiwa T.：“克拉霉素通过 AP 抑制脂多糖诱导的人单核细胞产生白细胞介素 8

萩原弘一: "抗菌タンパク質 その多様性と自然免疫における役割"最新医学. 57・8. 130-134 (2002)

Koichi Hagiwara：“抗菌蛋白：它们的多样性和在先天免疫中的作用”现代医学 57・8（2002）。

Pradono et al.: "Gene transfer of thromboxane A(2) synthase and prostaglandin I(2) synthase antithetically altered tumor angiogenesis and tumor growth"Cancer Research. 62. 63-66 (2002)

Pradono 等人：“血栓素 A(2) 合酶和前列腺素 I(2) 合酶的基因转移相反地改变了肿瘤血管生成和肿瘤生长”癌症研究。

Hagiwara et al.: "Mouse SWAM1 and SWAM2 are antibacterial proteins composed of a single whey acidic protein (WAP) motif."Journal of Immunology. 170. 1973-1980 (2003)

Hagiwara 等人：“小鼠 SWAM1 和 SWAM2 是由单个乳清酸性蛋白 (WAP) 基序组成的抗菌蛋白。”免疫学杂志。

Hagiwara K. et al.: "Mouse SWAM1 and SWAM2 are antibacterial proteins composed of a single whey acidic motif"Journal of Immunology. (in press).

Hagiwara K. 等人：“小鼠 SWAM1 和 SWAM2 是由单个乳清酸性基序组成的抗菌蛋白”《免疫学杂志》。