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Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 BMC+Musculoskelet+Disord 2016 ; 17 (1): ä Nephropedia Template TP
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Prokineticin 2 antagonist, PKRA7 suppresses arthritis in mice with collagen-induced arthritis #MMPMID27609223
Ito H; Noda K; Yoshida K; Otani K; Yoshiga M; Oto Y; Saito S; Kurosaka D
BMC Musculoskelet Disord 2016[]; 17 (1): ä PMID27609223show ga
Background: Prokineticin 2 (PK2) expression is upregulated in mice with collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. The purpose of our study was to investigate the effects of PK2 inhibition on CIA. Methods: PK2, prokineticin receptor (PKR) 1, and PKR2 mRNA transcripts in the joints of CIA mice were measured by real-time PCR on Days 21, 28, and 35 (n?=?15/day). Localization of PKR1 and PKR2 proteins was examined immunohistochemically. PKRA7, a PK2 antagonist, was administered intraperitoneally for 2 weeks to CIA mice, and the severity of arthritis was compared between treated (n?=?12) and untreated (n?=?12) mice. The gene expression levels of inflammatory cytokines IL-1?, IL-6, TNF-?, and VEGF were also measured by real-time PCR and compared between treated (n?=?6) and untreated (n?=?6) CIA mice. The data was statistically analyzed, and P values of less than 0.05 were considered significant. Results: In the thickened synovial membrane, PKR1 protein was expressed in infiltrating neutrophils, while PKR2 expression was found in macrophage-like mononuclear cells. PK2 gene expression was significantly more pronounced on Days 28 and 35 than on Day 21 (2.15 and 2.03 versus 1.00, P?=?0.0311 and 0.0247; Dunn?s multiple comparison). PKR2 gene expression levels were significantly higher on Days 28 and 35 compared to Day 21 (25.4 and 39.3 versus 1.0, P?=?0.002 and?0.0001; Dunn?s multiple comparison). Administration of PKRA7 suppressed the severity of arthritis (P?0.001; two-way analysis of variance). A gene expression analysis of inflammatory cytokines revealed significantly reduced IL-1? and lL-6 expression in the joints of PKRA7-treated mice compared to untreated mice (0.1 versus 1.0, P?=?0.0043 and 0.04 versus 1.0, P?=?0.0022, respectively; Mann-Whitney test). Conclusions: PK2 inhibition suppressed arthritis in mice with CIA.