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

Abstract

BackgroundProkineticin 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.MethodsPK2, 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.ResultsIn 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).ConclusionsPK2 inhibition suppressed arthritis in mice with CIA.

Activation of the NLRP3 Inflammasome Pathway by Prokineticin 2 in Testicular Macrophages of Uropathogenic Escherichia coli- Induced Orchitis

“…(18). PKR-A was also administered in an animal model of collagen-induced arthritis (31) and autoimmune encephalomyelitis (32). In our UPEC-infected model, IL-1β secretion and caspase-1 cleavage were decreased after PKR-A treatment.…”

Anti‑inflammatory effects of gambogic acid in murine collagen‑induced arthritis through PI3K/Akt signaling pathway

“…This study gained ethical approval from Chinese Traditional Medicine (Wenzhou, China). Arthritis was induced and emulsified in complete Freund's adjuvant and injected intradermally into the tail with 200 µg of collagen II (14). Meanwhile, in treatment with gambogic acid group, mice were treatment with 2 mg/kg/3 day (intraperitoneal injection) for 28 days (15).…”

Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression

“…A previous study demonstrated that PKRA7 is a PROK2 antagonist, which blocking the PROK2 expression, and consequently suppressing the tumorigenic and angiogenesis abilities of PROK2 and its downstream significantly pathways in glioma and pancreatic cells [ 10 ]. In another study, PKRA7 was administered intraperitoneally into collagen-induced arthritis (CIA) mice, and significantly inhibited the severity of arthritis [ 26 ]. Based on these evidences, PKRA7 as a candidate target reagent for cancer therapy.…”