The role of HMGB1 in the pathogenesis of rheumatic disease

Biochimica Et Biophysica Acta
Ulf Andersson, Helena E Harris

Abstract

HMGB1 is a ubiquitous nuclear protein that can be released by any damaged cell or by activated macrophages and certain other cell types. HMGB1 has been successfully therapeutically targeted in multiple preclinical models of infectious and sterile diseases including arthritis. Extracellular HMGB1 mediates inflammation via induction of cytokine and metalloproteinase production and recruitment and activation of dendritic cells needed for priming of naïve T helper type 1 lymphocytes. HMGB1 can bind endogenous molecules such as IL-1beta and nucleosomes and exogenous agents like endotoxin and microbial DNA. These complexes synergistically increase the capacity for activation of adaptive and innate immunity. HMGB1-nucleosome complexes induce autoantibody formation against double-stranded DNA and nucleosomes, which does not occur if HMGB1 is absent. These antibodies are central in the pathogenesis of systemic lupus erythematosus and patients with active disease have both increased HMGB1 and HMGB1-nucleosome levels in circulation. Furthermore, HMGB1 is strongly bipolar charged, enabling cell membrane passage and intracellular transport of complexed molecules including DNA. Rheumatoid arthritis patients have excessive extracellular HMGB1...Continue Reading

Associated Clinical Trials

Citations

Sep 14, 2010·Cell and Tissue Research·Alessandra CastiglioniAngelo A Manfredi
Mar 22, 2013·Current Rheumatology Reports·Ru Liu-Bryan
Dec 7, 2010·Immunologic Research·David S PisetskyAnirudh J Ullal
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Huan YangKevin J Tracey
Mar 1, 2012·The Journal of Experimental Medicine·Milena SchiraldiMariagrazia Uguccioni
Jul 25, 2012·Journal of Neuroinflammation·Polina FeldmanFletcher A White
Feb 22, 2012·Arthritis Research & Therapy·Agneta ZickertIva Gunnarsson
Apr 14, 2010·Molecular Medicine·Hanna SchierbeckHelena Erlandsson Harris
Jan 5, 2011·Frontiers in Bioscience (Scholar Edition)·Zheng Zhou, Wen-Cheng Xiong
Nov 14, 2013·Pharmacology & Therapeutics·Domenica MusumeciDaniela Montesarchio
Aug 3, 2013·Brain & Development·Hiroshi MomonakaTakashi Ichiyama
Mar 13, 2012·Biochemical and Biophysical Research Communications·Bernhard MoserJan Ankersmit
Dec 5, 2012·Molecular Immunology·Emilie VenereauMarco E Bianchi
Apr 7, 2012·Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association·Lars EnochsonAnders Lindahl
Jun 5, 2012·Clinical Immunology : the Official Journal of the Clinical Immunology Society·David S Pisetsky
May 24, 2011·The International Journal of Biochemistry & Cell Biology·Geum-Hwa LeeHyung-Ryong Kim
May 10, 2011·Molecular Immunology·Trent M WoodruffFrancesco Tedesco
May 21, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·Manasi MajumdarMini P Singh
Dec 25, 2010·British Journal of Pharmacology·Jamie CampbellMatthew A Sleeman
Nov 26, 2010·British Journal of Pharmacology·Konstantin TsoyiKi Churl Chang
Jul 11, 2014·Molecular Aspects of Medicine·Rui KangDaolin Tang
Dec 3, 2014·Microbes and Infection·Timea Pálmai-Pallag, Csanád Z Bachrati
Oct 11, 2011·Rheumatology·Fui G Goh, Kim S Midwood
May 13, 2017·Expert Opinion on Therapeutic Targets·Judith AustermannJohannes Roth
Sep 24, 2016·Joint, Bone, Spine : Revue Du Rhumatisme·Miha LavricHelmut Wittkowski
Dec 23, 2017·Inflammatory Bowel Diseases·Mirko Di RuscioGiovanni Latella
Jul 27, 2011·The American Journal of Gastroenterology·Roberta VitaliSalvatore Cucchiara
Apr 3, 2019·International Journal of Rheumatic Diseases·Elham HossnyAyman Ashour
Feb 18, 2014·Molecular Medicine·Melinda Magna, David S Pisetsky
Apr 7, 2011·Nature Reviews. Rheumatology·Mei Zong, Ingrid E Lundberg

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.