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

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posted on 23.10.2012 by Sivasakthivel Thirugnanam, Gnanasekar Munirathinam, Anandharaman Veerapathran, Gajalakshmi Dakshinamoorthy, Maryada V. Reddy, Kalyanasundaram Ramaswamy
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 proinflammatory B box domain of human HMGB1. When incubated with mouse peritoneal macrophages and human promyelocytic leukemia cells, rBmHMGB1 induced secretion of significant levels of proinflammatory 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.

Funding

This study was funded by NIH RO1 grant (AI064745). The authors would like to thank Dr. Steven Williams, Smith College, Northampton, MA for providing us W. bancrofti and B. malayi cDNA libraries. The authors would also like to thank NIAID/NIH Filariasis Research Reagent Resource Center (FR3) at the University of Georgia, Athens, GA for providing parasite materials for this study.

History

Publisher Statement

This is a copy of an article published in Parasitology Research © 2012 Springer Verlag. The original publication is available at www.springerlink.com DOI: 10.1007/s00436-012-2878-x

Publisher

Springer Verlag

Language

en_US

issn

0932-0113

Issue date

01/01/2012

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