GWAS-identified hyperuricemia-associated IGF1R variant rs6598541 has a limited role in urate mediated inflammation in human mononuclear cells.

Autor: Gaal, Orsolya I., Liu, Ruiqi, Marginean, Dragoș, Badii, Medeea, Cabău, Georgiana, Hotea, Ioana, Nica, Valentin, Colcear, Doina, HINT Consortium, Joosten, Leo A. B., Pop, Ioan V., Crişan, Tania O., Farcaş, Marius, Marginean, Dragoş H., Badii, Medeea O., Peca, Loredana, Mirea, Andreea-Manuela, Pop, Mariana S., Rus, Ancuta, Pamfil, Cristina
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Zdroj: Scientific Reports; 2/16/2024, Vol. 14 Issue 1, p1-9, 9p
Abstrakt: Gout is a common autoinflammatory joint diseases characterized by deposition of monosodium urate (MSU) crystals which trigger an innate immune response mediated by inflammatory cytokines. IGF1R is one of the loci associated with both urate levels and gout susceptibility in GWAS to date, and IGF-1-IGF-1R signaling is implicated in urate control. We investigate the role of IGF-1/IGF1R signaling in the context of gouty inflammation. Also, we test the gout and urate-associated IGF1R rs6598541 polymorphism for association with the inflammatory capacity of mononuclear cells. For this, freshly isolated human peripheral blood mononuclear cells (PBMCs) were exposed to recombinant IGF-1 or anti-IGF1R neutralizing antibody in the presence or absence of solubilized urate, stimulated with LPS/MSU crystals. Also, the association of rs6598541 with IGF1R and protein expression and with ex vivo cytokine production levels after stimulation with gout specific stimuli was tested. Urate exposure was not associated with IGF1R expression in vitro or in vivo. Modulation of IGF1R did not alter urate-induced inflammation. Developing urate-induced trained immunity in vitro was not influenced in cells challenged with IGF-1 recombinant protein. Moreover, the IGF1R rs6598541 SNP was not associated with cytokine production. Our results indicate that urate-induced inflammatory priming is not regulated by IGF-1/IGF1R signaling in vitro. IGF1R rs6598541 status was not asociated with IGF1R expression or cytokine production in primary human PBMCs. This study suggests that the role of IGF1R in gout is tissue-specific and may be more relevant in the control of urate levels rather than in inflammatory signaling in gout. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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