Title:HMGB-1 as a Target for Inflammation Controlling
Volume: 6
Issue: 3
Author(s): Jose A. Nogueira-Machado and Caroline M. de Oliveira Volpe
Affiliation:
Keywords:
Cytokines, HMGB-1, inflammation, patents, RAGE, TLR2/4.
Abstract: In the present study, we evaluated recent patents that describe products or methods able to down-regulate the
pro-inflammatory action of HMGB-1, also called as amphoterin. High Mobility Group Box-1 (HMGB-1) has been implicated
in the pathogenesis of inflammatory diseases. HMGB-1 has been proposed to be a crucial mediator in the pathogenesis
of many diseases including sepsis, arthritis, cancer, autoimmunity diseases and diabetes. It has been suggested that
HMGB-1 itself can signal through RAGEs (receptor for advanced glycation end products) and through the Toll-Like Receptors
TLR2 and TLR4. Activation of these receptors results ultimately in the activation of Nuclear Factor-kappaB (NFkappaB),
inducing the up-regulation of leukocyte adhesion molecules, production of pro-inflammatory cytokines and angiogenic
factors in both hematopoietic and endothelial cells, thereby promoting inflammation. There are several patents
proposed for controlling the production, secretion and neutralization of HMGB-1 and consequently the inflammatory
process. We have divided the patents in six groups based on mechanism of action. The group 1 is associated with inhibition
of HMGB-1 using anti-HMGB-1 antibodies; group 2: inhibition of HMGB-1 releases from the nucleus into the extracellular
space; group 3: HMGB-A box as a competitive antagonist of HMGB-1; group 4: blockage of RAGE-HMGB-1
signaling using RAGE antagonists; group 5: blockage of TLR-HMGB-1 signaling using anti-TLR2 antibodies and group
6: other molecules that modulate HMGB-1 activity using e.g. human soluble thrombomodulin. The mechanism of
HMGB-1 action, its role and efficiency of each group of patents proposed for controlling inflammation are discussed.
