title: HMGB-1 as a target for inflammation controlling.
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.
authors: Núcleo de Pós Graduação e Pesquisa (NPGP), Hospital Santa Casa de Misericórdia de Belo Horizonte - Belo Horizonte-MG-Brazil. aunog.bh@terra.com.br
authors: Jose A
authors: JA
authors: Nogueira-Machado
authors: Caroline M
authors: CM
authors: de Oliveira Volpe
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000906:Antibodies / Q000627:therapeutic use; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D010330:Patents as Topic; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D018180:Thrombomodulin / Q000627:therapeutic use; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D018180:Thrombomodulin; D051195:Toll-Like Receptor 2