High-mobility group box 1 (
HMGB1), a highly conserved
DNA-binding protein, plays an important role in maintaining
nucleosome structures, transcription, and
inflammation. We identified a homolog of
HMGB1 in the Japanese lamprey (Lampetra japonica). The Lampetra japonica
HMGB1 gene (Lj-HMGB1) has over 70% sequence identity with its homologs in jawed vertebrates. Despite the reasonably high sequence identity with other
HMGB1 proteins, Lj-HMGB1 did not group together with these
proteins in a phylogenetic analysis. We examined Lj-HMGB1 expression in lymphocyte-like cells, and the kidneys, heart, gills, and intestines of lampreys before and after the animals were challenged with
lipopolysaccharide (LPS) and
concanavalin A (ConA). Lj-HMGB1 was initially expressed at a higher level in the heart, but
after treatment with LPS and ConA only the gills demonstrated a significant up-regulation of expression. The recombinant Lj-HMGB1 (rLj-HMGB1)
protein bound
double-stranded DNA and induced the proliferation of human
adenocarcinoma cells to a similar extent as human
HMGB1. We further revealed that Lj-HMGB1 was able to induce the production of
tumor necrosis factor-α (TNF-α), a pro-inflammatory mediator, in activated human
acute monocytic leukemia cells. These results suggest that lampreys use
HMGB1 to activate their innate immunity for the purpose of pathogen defense.