title: Cloning and characterization of high mobility group box protein 1 (HMGB1) of Wuchereria bancrofti and Brugia malayi.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA.
authors.forename: Sivasakthivel
authors.initials: S
authors.lastname: Thirugnanam
authors.forename: Gnanasekar
authors.initials: G
authors.lastname: Munirathinam
authors.forename: Anandharaman
authors.initials: A
authors.lastname: Veerapathran
authors.forename: Gajalakshmi
authors.initials: G
authors.lastname: Dakshinamoorthy
authors.forename: Maryada V
authors.initials: MV
authors.lastname: Reddy
authors.forename: Kalyanasundaram
authors.initials: K
authors.lastname: Ramaswamy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017178:Brugia malayi / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D019295:Computational Biology; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D011994:Recombinant Proteins; D014958:Wuchereria bancrofti / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; D011994:Recombinant Proteins