Cloning and characterization of a high mobility group box 1 (HMGB1) homologue protein from Schistosoma mansoni.
Mammalian homologue of high mobility group box chromatin protein (HMGB) 1 was identified and cloned from human parasites, Schistosoma mansoni and S. haematobium. Sequence analyses showed that the parasite HMGB1s has 35-40% identity to human and rodent HMGB1s, and 33% identity to Caenorhabditis elegans HMGB1. Parasite HMGB1s also contains an A box and B box domain similar to mammalian HMGB1, however, it lacks the C-terminal tail that is present in mammalian HMGB1s. Analysis of the expression of HMGB1 in various life cycle stages of S. mansoni reveal S. mansoni HMGB1 (SmHMGB1) as a stage-specific protein, expressed abundantly in egg and adult female stages and at moderate levels in skin-stage schistosomula. Significant levels of SmHMGB1 were also present in excretory secretions of egg stages. Subsequent characterization studies showed that SmHMGB1 is a potent inducer of pro-inflammatory cytokines such as TNFalpha, IL-1Ralpha, IL-2Ralpha, IL-6, IL-13, IL-13Ralpha1, IL-15 and MIP-1alpha from mouse peritoneal macrophages. Pro-inflammatory activity, especially production of TNFalpha-inducing activity, appears to be a function of the B box domain protein. This was confirmed by both real-time reverse transcription PCR and by cytokine ELISA. Thus, results presented in this study suggest that SmHMGB1 may be a key molecule in the development of host inflammatory immune responses associated with schistosomiasis.
Gnanasekar
Munirathinam
M
Department of Biomedical Sciences, University of Illinois College of Medicine, 1601 Parkview Avenue, Rockford, IL 61107, USA.
Velusamy
Rangasamy
R
He
Yi-Xun
YX
Ramaswamy
Kalyanasundaram
K
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D018507:Gene Expression Regulation, Developmental; D024243:HMGB1 Protein / Q000235:genetics* / Q000276:immunology; D015801:Helminth Proteins / Q000235:genetics*; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012548:Schistosoma haematobium / Q000235:genetics; D012550:Schistosoma mansoni / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D016207:Cytokines; D018509:DNA, Helminth; D024243:HMGB1 Protein; D015801:Helminth Proteins; D012333:RNA, Messenger