1. Mechanism of Action of Colchicine in the Treatment of Gout
Nicola Dalbeth, MD, Thomas J. Lauterio, PhD, MBA, Henry R. Wolfe, PhD 
Clinical Therapeutics 
Volume 36, Issue 10, Pages (October 2014)
DOI: /j.clinthera
Copyright © 2014 The Authors Terms and Conditions

2. Figure
Mechanisms of monosodium urate (MSU) crystal–mediated inflammation in acute gouty arthritis. (1) MSU crystals interact with the surface of dendritic cells through crystal-lipid contact in a manner that does not rely on specific cell surface receptors. Lipid bilayer perturbation may trigger an intracellular signaling cascade, leading to spleen tyrosine kinase (Syk) activation and additional dendritic cell activation.8 (2) MSU crystals bind to Toll-like receptors (TLRs). In the presence of myeloid differentiation factor 88 (MyD88), nuclear factor (NF)-κB is induced and pro-inflammatory molecules are released. The expression of multiple adhesion molecules on the surface of endothelial cells is increased. (3) MSU crystal phagocytosis leads to phagolysosomal damage, which leads to potassium efflux. The addition of available reactive oxygen species (ROS), ASC, and pro-caspase-1 to the nucleotide-binding domain, leucine-rich repeat-containing 3 (NLR3) receptor forms the NLRP3 inflammasome complex, which induces interleukin (IL)-1β. ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; TNF, tumor necrosis factor.
Clinical Therapeutics  , DOI: ( /j.clinthera )
Copyright © 2014 The Authors Terms and Conditions