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BMC Musculoskelet Disord. 2016 Sep 8;17:387. doi: 10.1186/s12891-016-1243-0.

Prokineticin 2 antagonist, PKRA7 suppresses arthritis in mice with collagen-induced arthritis.

Author information

1
Division of Rheumatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, Japan.
2
Division of Molecular Immunology, Research Center for Medical Sciences, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, Japan.
3
Division of Rheumatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, Japan. d_kurosaka@jikei.ac.jp.

Abstract

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-1β, IL-6, TNF-α, 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-1β 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.

KEYWORDS:

Collagen-induced arthritis; PKRA7; Prokineticin 2; Prokineticin antagonist; Prokineticin receptor 1; Prokineticin receptor 2

PMID:
27609223
PMCID:
PMC5016855
DOI:
10.1186/s12891-016-1243-0
[Indexed for MEDLINE]
Free PMC Article

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