transforming-growth-factor-beta and Arthritis--Gouty

Recent advances have stimulated new interest in the area of crystal arthritis, as microcrystals can be considered to be endogenous "danger signals" and are potent stimulators of immune as well as non-immune cells. The best known microcrystals include urate (MSU), and calcium pyrophosphate (CPP) crystals, associated with gout and pseudogout, respectively. Acute inflammation is the hallmark of the acute tissue reaction to crystals in both gout and pseudogout. The mechanisms leading to joint inflammation in these diseases involve first crystal formation and subsequent coating with serum proteins. Crystals can then interact with plasma cell membrane, either directly or via membrane receptors, leading to NLRP3 activation, proteolytic cleavage and maturation of pro-interleukin-1β (pro-IL1β) and secretion of mature IL1β. Once released, this cytokine orchestrates a series of events leading to endothelial cell activation and neutrophil recruitment. Ultimately, gout resolution involves several mechanisms including monocyte differentiation into macrophage, clearance of apoptotic neutrophils by macrophages, production of Transforming Growth Factor (TGF-β) and modification of protein coating on the crystal surface. This review will examine these different steps.

Topics: Apoptosis; Arthritis, Gouty; Biomarkers; Calcium Phosphates; Carrier Proteins; Chondrocalcinosis; Endothelial Cells; Gout; Humans; Inflammasomes; Inflammation; Interleukin-1beta; Macrophages; Neutrophils; NLR Family, Pyrin Domain-Containing 3 Protein; Proteolysis; Transforming Growth Factor beta; Uric Acid

Gout inflammation is an acute and self-resolving reaction. MSU crystals can stimulate cells through either crystal-cell membrane interaction or after their phagocytosis. The onset of gout inflammation relies on non-hematopoietic resident cells whereas the amplification of the reaction is driven by phagocytic cells of immune innate system. Interleukin-1β (IL-1β) and polynuclear neutrophils play central role in gout inflammation. In vitro, MSU crystal-induced IL-1β secretion is secondary mainly to NLRP3 inflammasome activation although numerous proteases are also involved. Mechanisms of NLRP3 inflammasome activation remain unclear involving mostly reactive oxygen species production. Gout resolution involves several mechanisms including monocyte differentiation into macrophage, clearance of apoptotic neutrophils by macrophages, production of Transforming Growth Factor (TGF-β) and modification of protein coating on MSU crystal surface.

Topics: Apoptosis; Arthritis, Gouty; Endocytosis; Humans; Immunity, Innate; Inflammation Mediators; Interleukin-1beta; Joints; Macrophages; Membrane Glycoproteins; Neutrophils; Phagocytosis; Receptors, Immunologic; Signal Transduction; Transforming Growth Factor beta; Triggering Receptor Expressed on Myeloid Cells-1; Uric Acid