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Review
. 2014 Jun;10(6):713-27.
doi: 10.1586/1744666X.2014.909730. Epub 2014 Apr 19.

Molecular mechanism and therapeutic modulation of high mobility group box 1 release and action: an updated review

Ben Lu  1 , Ce Wang, Mao Wang, Wei Li, Fangping Chen, Kevin J Tracey, Haichao Wang
Affiliations
Review

Molecular mechanism and therapeutic modulation of high mobility group box 1 release and action: an updated review

Ben Lu et al. Expert Rev Clin Immunol. 2014 Jun.

Abstract

High mobility group box 1 (HMGB1) is an evolutionarily conserved protein, and is constitutively expressed in virtually all types of cells. Infection and injury converge on common inflammatory responses that are mediated by HMGB1 secreted from immunologically activated immune cells or passively released from pathologically damaged cells. Herein we review the emerging molecular mechanisms underlying the regulation of pathogen-associated molecular patterns (PAMPs)-induced HMGB1 secretion, and summarize many HMGB1-targeting therapeutic strategies for the treatment of infection- and injury-elicited inflammatory diseases. It may well be possible to develop strategies that specifically attenuate damage-associated molecular patterns (DAMPs)-mediated inflammatory responses without compromising the PAMPs-mediated innate immunity for the clinical management of infection- and injury-elicited inflammatory diseases.

Keywords: damage-associated molecular patterns; herbal components; high mobility group box 1; infection; injury; pathogen-associated molecular patterns; signaling.

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Figures

Figure 1
Figure 1. Pathogen-associated molecular patterns (PAMPs) induced active HMGB1 secretion and possibly passive release
The functional domains of human HMGB1 are noted.
Figure 2
Figure 2. A microbial infection triggers a systemic inflammatory response mediated by HMGB1 secreted by immunologically activated innate immune cells and pathologically damaged cells
Microbial invasion leads to the libration of PAMPs, which trigger active HMGB1 secretion and passive release. Extracellular HMGB1 then amplifies the rigorous inflammatory responses by facilitating leukocyte recruitment and activation, resulting in cytokine storm and organ dysfunction. Note the immunological activities are modulated by the redox status in a divergent fashion.
Figure 3
Figure 3. Chemical structures of HMGB1-inhibiting herbal components
Note the chemical structural similarly between two PKR inhibiting agents: CBX and 7DG.
See this image and copyright information in PMC

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