High mobility group box 1 (
HMGB1) protein is released from cells as a pro-inflammatory
cytokine in response to an injury or
infection. During
dengue hemorrhagic fever (DHF)/
dengue shock syndrome (DSS), a number of pro-inflammatory
cytokines are released, contributing to disease pathogenesis. In this study, the release of
HMGB1 from human
myelogenous leukemia cell line K562 and primary peripheral blood monocytes (
PBM) cells was examined during dengue virus (DV)-
infection.
HMGB1 was shown to translocate from cell nuclei to the cytoplasm in both K562- and
PBM-infected cells. The translocation of
HMGB1 from the nucleus to the cytoplasm was shown to be mediated by the host cell p300/CBP-associated factor (
PCAF) acetylase complex in K562 cells. In addition, DV
capsid protein was observed to be the putative
viral protein in actuating
HMGB1 migration from the nucleus to cytoplasm through the involvement of
PCAF acetylase.
HMGB1 was released from DV-infected K562 cells into the extracellular milieu in a multiplicity of
infection (M.O.I.)-independent manner and its release can be inhibited by the addition of 1-5 mM of
ethyl pyruvate (EP) in a dose-dependent manner. Application of DV-infected K562 cell culture supernatants to primary endothelial cells induced vascular permeability. In contrast, supernatants from DV-infected K562 cells treated with EP or
HMGB1 neutralizing antibody were observed to maintain the structural integrity of the vascular barrier.