The proteasome: a central regulator of inflammation and macrophage function.
Proteasomes, multisubunit complexes that consist of a 20S proteasome and a 19S regulatory complex, are essential for several cellular processes. Our interest in the proteasome complex stems from our observations that a novel photoactivable lipopolysaccharide (LPS) probe binds to specific proteasome subunits, and that LPS enhances the chymotrypsin-like activity of the proteasome to degrade synthetic peptides in vitro. Experiments with proteasome inhibitors have shown that expression of many LPS-inducible genes, including TLR2, is inhibited in macrophages. More important, proteasome inhibitors such as lactacystin can prevent LPS-induced shock in mice. This article focuses on the role of the proteasome in the development of inflammatory processes, which may result in septic shock, hemorrhagic shock, atherosclerosis, and neurodegenerative disorders. Taken collectively, the results suggest a potentially important role of the proteasome in inflammation and other macrophage functions.
Qureshi
Nilofer
N
Department of Basic Medical Science, School of Medicine, Shock/Trauma Research Center, University of Maryland-Baltimore, Baltimore, MD, USA. qureshin@umkc.edu
Vogel
Stefanie N
SN
Van Way
Charles
C
Papasian
Christopher J
CJ
Qureshi
Asaf A
AA
Morrison
David C
DC
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000375:Aging / Q000276:immunology; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology; D002784:Cholesterol / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D051379:Mice; D019636:Neurodegenerative Diseases / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D061988:Proteasome Inhibitors; D012771:Shock, Hemorrhagic / Q000276:immunology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis
D008070:Lipopolysaccharides; D061988:Proteasome Inhibitors; D051195:Toll-Like Receptor 2; C067713:lactacystin; D002784:Cholesterol; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine