Cloning and characterization of high mobility group box protein 1 (HMGB1) of Wuchereria bancrofti and Brugia malayi.

Cloning and characterization of high mobility group box protein 1 (HMGB1) of Wuchereria bancrofti and Brugia malayi.
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DOI:
10.1007/s00436-012-2878-x
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发表时间:
2012-08
影响因子:
2
通讯作者:
Ramaswamy K
Ramaswamy K
中科院分区:
医学3区
文献类型:
--
作者:
Thirugnanam S;Munirathinam G;Veerapathran A;Dakshinamoorthy G;Reddy MV;Ramaswamy K

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从班氏吴策线虫和马来丝虫中克隆了高迁移率族蛋白1(HMGB 1)的同源蛋白。序列分析表明,W. Bancrofti HMGB 1(WbHMGB 1)和B.马来人HMGB 1(BmHMGB 1)蛋白具有99%的序列同一性。丝虫HMGB 1显示出HMGB蛋白家族典型的结构序列特征,仅由单个HMG盒结构域组成,该结构域与人HMGB 1的促炎性B盒结构域具有显着的序列相似性。当与小鼠腹腔巨噬细胞和人早幼粒细胞白血病细胞孵育时,rBmHMGB 1诱导显著水平的促炎细胞因子(如TNF-α、GM-CSF和IL-6)分泌。功能分析还表明,丝虫HMGB 1蛋白可以与超螺旋DNA结合,类似于其他HMG蛋白家族。BmHMGB 1蛋白在寄生虫的成虫和微丝蚴阶段表达,并在活寄生虫的排泄分泌物中发现。这些发现表明,丝虫HMGB 1可能在淋巴丝虫病相关的淋巴病理学中发挥重要作用。
A human homologue of high mobility group box 1 (HMGB1) protein was cloned and characterized from the human filarial parasites Wuchereria bancrofti and Brugia malayi. Sequence analysis showed that W. bancrofti HMGB1 (WbHMGB1) and B. malayi HMGB1 (BmHMGB1) proteins share 99 % sequence identity. Filarial HMGB1 showed typical architectural sequence characteristics of HMGB family of proteins and consisted of only a single HMG box domain that had significant sequence similarity to the pro-inflammatory B box domain of human HMGB1. When incubated with mouse peritoneal macrophages and human promyelocytic leukemia cells, rBmHMGB1 induced secretion of significant levels of pro-inflammatory cytokines such as TNF-α, GM-CSF, and IL-6. Functional analysis also showed that the filarial HMGB1 proteins can bind to supercoiled DNA similar to other HMG family of proteins. BmHMGB1 protein is expressed in the adult and microfilarial stages of the parasite and is found in the excretory secretions of the live parasites. These findings suggest that filarial HMGB1 may have a significant role in lymphatic pathology associated with lymphatic filariasis.
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