Myeloid-Related Proteins 8 and 14 Contribute to Monosodium Urate Monohydrate Crystal-Induced Inflammation in Gout.

Autor:	Holzinger, Dirk, Nippe, Nadine, Vogl, Thomas, Marketon, Kristina, Mysore, Vijayashree, Weinhage, Toni, Dalbeth, Nicola, Pool, Bregina, Merriman, Tony, Baeten, Dominique, Ives, Annette, Busso, Nathalie, Foell, Dirk, Bas, Sylvette, Gabay, Cem, Roth, Johannes
Předmět:	ACADEMIC medical centers ANALYSIS of variance ANIMAL experimentation ENZYME-linked immunosorbent assay GOUT IMMUNOHISTOCHEMISTRY INFLAMMATION MICE POLYMERASE chain reaction PROTEINS RESEARCH funding STATISTICS T-test (Statistics) WESTERN immunoblotting DATA analysis REVERSE transcriptase polymerase chain reaction
Zdroj:	Arthritis & Rheumatology; May2014, Vol. 66 Issue 5, p1327-1339, 13p
Abstrakt:	Objective Monosodium urate monohydrate (MSU) crystal-induced interleukin-1β (IL-1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL-1β-inducing factor, MSU crystals alone are insufficient to induce IL-1β secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known. We undertook this study to analyze the costimulatory properties of myeloid-related protein 8 (MRP-8) and MRP-14 (endogenous Toll-like receptor 4 [TLR-4] agonists) in MSU crystal-induced IL-1β secretion and their relevance in gout. Methods MRP-8/MRP-14 was measured in paired serum and synovial fluid samples by enzyme-linked immunosorbent assay (ELISA) and localized in synovial tissue from gout patients by immunohistochemistry. Serum levels were correlated with disease activity, and MSU crystal-induced release of MRPs from human phagocytes was measured. Costimulatory effects of MRP-8 and MRP-14 on MSU crystal-induced IL-1β secretion from phagocytes were analyzed in vitro by ELISA, Western blotting, and polymerase chain reaction. The impact of MRP was tested in vivo in a murine MSU crystal-induced peritonitis model. Results MRP-8/MRP-14 levels were elevated in the synovium, tophi, and serum of patients with gout and correlated with disease activity. MRP-8/MRP-14 was released by MSU crystal-activated phagocytes and increased MSU crystal-induced IL-1β secretion in a TLR-4-dependent manner. Targeted deletion of MRP-14 in mice led to a moderately reduced response of MSU crystal-induced inflammation in vivo. Conclusion MRP-8 and MRP-14, which are highly expressed in gout, are enhancers of MSU crystal-induced IL-1β secretion in vitro and in vivo. These endogenous TLR-4 ligands released by activated phagocytes contribute to the maintenance of inflammation in gout. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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