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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

PKRA7 as an antagonist of PK2. PK2 binds to PKR1 and PKR2 receptors and regulates various physiological processes, including angiogenesis, chemotaxis, immune polarization, and circadian rhythm. PKRA7 also binds to PKR1 and PKR2 and competitively blocks the binding of PK2
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC5016855&req=5

Fig1: PKRA7 as an antagonist of PK2. PK2 binds to PKR1 and PKR2 receptors and regulates various physiological processes, including angiogenesis, chemotaxis, immune polarization, and circadian rhythm. PKRA7 also binds to PKR1 and PKR2 and competitively blocks the binding of PK2

Mentions: PKRA7 is a small molecular inhibitor developed by Curtis et al. by substitution of alanine with methionine and addition of methionine at the N-terminus of PK2; the mutated peptide mimics PK2 and competitively blocks PK2-PKR1/2 interactions [19] (Fig. 1). The researchers showed that this molecule inhibits angiogenesis and macrophage infiltration in mice transplanted with glioblastoma and pancreatic cancer, respectively [19]. The primary goal of our study was to investigate the effects of PKRA7 on arthritis using the mouse model with CIA.Fig. 1


Prokineticin 2 antagonist, PKRA7 suppresses arthritis in mice with collagen-induced arthritis
PKRA7 as an antagonist of PK2. PK2 binds to PKR1 and PKR2 receptors and regulates various physiological processes, including angiogenesis, chemotaxis, immune polarization, and circadian rhythm. PKRA7 also binds to PKR1 and PKR2 and competitively blocks the binding of PK2
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5016855&req=5

Fig1: PKRA7 as an antagonist of PK2. PK2 binds to PKR1 and PKR2 receptors and regulates various physiological processes, including angiogenesis, chemotaxis, immune polarization, and circadian rhythm. PKRA7 also binds to PKR1 and PKR2 and competitively blocks the binding of PK2
Mentions: PKRA7 is a small molecular inhibitor developed by Curtis et al. by substitution of alanine with methionine and addition of methionine at the N-terminus of PK2; the mutated peptide mimics PK2 and competitively blocks PK2-PKR1/2 interactions [19] (Fig. 1). The researchers showed that this molecule inhibits angiogenesis and macrophage infiltration in mice transplanted with glioblastoma and pancreatic cancer, respectively [19]. The primary goal of our study was to investigate the effects of PKRA7 on arthritis using the mouse model with CIA.Fig. 1

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus