A non-peptide CCR5 antagonist inhibits collagen-induced arthritis by modulating T cell migration without affecting anti-collagen T cell responses

Yang, Yi; Mukai, Takahiro; Gao, Ping; Yamaguchi, Norihiko; Ono, Shiro; Iwaki, Hiroshi; Obika, Satoshi; Imanishi, Takeshi; Tsujimura, Takahiro; Hamaoka, Toshiyuki; Fujiwara, Hiromi

doi:10.1002/1521-4141(200208)32:8<2124::aid-immu2124>3.0.co;2-s

Cited by 115 publications

(90 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In that respect, it is interesting that CCR5 blockade leads to inhibition of collagen-induced arthritis, an animal model of RA. 27,28 …”

Section: Ccr5-d32 Polymorphism and Ra S Prahaladmentioning

confidence: 99%

Negative association between the chemokine receptor CCR5-Δ32 polymorphism and rheumatoid arthritis: a meta-analysis

Prahalad

2006

Genes Immun

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is characterized by synovial inflammation mediated by T-cells, monocytes and macrophages. The homing of these cells to the inflamed synovium is regulated by chemokine-receptors and their ligands. A 32-basepair deletion (D32) in the gene encoding CCR5, a chemokine-receptor, results in a non-functional receptor. A negative association between CCR5-D32 and RA has been described, although other studies found no associations. Furthermore, the observation that individuals homozygous for CCR5-D32 develop RA has raised questions about the role of CCR5-D32. This meta-analysis of all published case-control association studies confirms the negative association between CCR5-D32 and RA (Odds Ratio ¼ 0.65; 95% confidence intervals ¼ 0.55-0.77; Po0.0001), suggesting that CCR5-D32 is protective against the development of RA. CCR5 blockade in animal models of RA results in amelioration of arthritis, suggesting that CCR5 blockade could also modify disease in patients with RA.

show abstract

“…In that respect, it is interesting that CCR5 blockade leads to inhibition of collagen-induced arthritis, an animal model of RA. 27,28 …”

Section: Ccr5-d32 Polymorphism and Ra S Prahaladmentioning

confidence: 99%

Negative association between the chemokine receptor CCR5-Δ32 polymorphism and rheumatoid arthritis: a meta-analysis

Prahalad

2006

Genes Immun

View full text Add to dashboard Cite

show abstract

“…Nonpeptide small molecule antagonists have been shown to interact with chemokine receptors, including CXCR3. For example, the CCR5 small molecule antagonist N, N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]tetrahydro-2H-pyran-4-aminium chloride (TAK779), also binds to murine, but not human, CXCR3 with high affinity and is effective in reducing severity and incidence of collageninduced arthritis in the DBA/1 mouse model (Yang et al, 2002;Gao et al, 2003). These proof-of-concept experiments have led to the development of specific small molecule antagonists for CXCR3, and one such compound (T487) is currently being developed for psoriasis and RA by ChemoCentryx, Inc. (Mountain View, CA) in collaboration with Tularik/Amgen Biologicals (Thousand Oaks, CA) (Medina and Johnson, 2002;Medina et al, 2004).…”

mentioning

confidence: 99%

Pharmacological Characterization of CXC Chemokine Receptor 3 Ligands and a Small Molecule Antagonist

Heise¹,

Pahuja²,

Hudson³

et al. 2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The CXC chemokine receptor 3 (CXCR3) is predominantly expressed on T helper type 1 (Th1) cells that are involved in inflammatory diseases. The three CXCR3 ligands CXCL9, CXCL10, and CXCL11 are produced at sites of inflammation and elicit migration of pathological Th1 cells. Here, we are the first to characterize the pharmacological potencies and specificity of a CXCR3 antagonist, N-1R- [3-(4-ethoxy-phenyl of 7 to 18 nM). NBI-74330 was selective for CXCR3 because it showed no significant inhibition of chemotactic responses to other chemokines and did not inhibit radioligand binding to a panel of nonchemokine G-protein coupled receptors. There was a striking difference in potencies among the three CXCR3 ligands, with CXCL11 Ͼ Ͼ CXCL10 Ͼ CXCL9. A comparison of the rank order of K i values with the rank order of monocyte production levels of these three ligands revealed a precise inverse correlation, suggesting that the weaker receptor affinities of CXCL9 and CXCL10 were physiologically compensated for by an elevated expression, perhaps to maintain effectiveness of each ligand under physiological conditions.

show abstract

“…Primary T cells were purified by immunomagnetic negative selection to delete B cells and I-A + APC as described previously [18] . Lymph node cells were allowed to react with anti-I-A d/b mAb and then incubated with magnetic particles bound to goat anti-mouse Ig (Polysciences, Inc, Eppelheim, Germany).…”

Section: Preparation Of Purified T Cells and Enriched Antigen Presentmentioning

confidence: 99%

“…Splenic antigen-presenting cell (APC)-enriched populations were separated using immunomagnetic negative selection to delete the surface Ig + cells (B cells) and T cells as described previously [18] . Splenocytes were allowed to react with a mixture of rat anti-mouse CD4 (GK1.5) and rat anti-mouse CD8 (2.43) mAb and then incubated with a mixture of magnetic particles bound to goat anti-rat (Advanced Magnetics, Cambridge, MA, USA) and goat anti-mouse Ig.…”

Section: Preparation Of Purified T Cells and Enriched Antigen Presentmentioning

confidence: 99%

Periplocoside A prevents experimental autoimmune encephalomyelitis by suppressing IL-17 production and inhibits differentiation of Th17 cells

Zhang

Chen

et al. 2009

Acta Pharmacol Sin

Self Cite

View full text Add to dashboard Cite

Aim: The aim of this study was to determine the therapeutic effect of Periplocoside A (PSA), a natural product isolated from the traditional Chinese herbal medicine Periploca sepium Bge, in MOG (myelin oligodendrocyte glycoprotein 35-55)-induced experimental autoimmune encephalomyelitis (EAE). Methods: Female C57BL/6 mice immunized with MOG 35-55 were treated with (50 mg/kg or 25 mg/kg) or without PSA following immunization and continuously throughout the study. The degree of CNS inflammation was evaluated by H&E staining. Anti-MOG-specific recall responses were analyzed by [ 3 H]-Thymidine incorporation, ELISA, and RT-PCR. The proportion of IL-17-producing T cells was measured by flow cytometry. Results: Oral administration of PSA significantly reduced the incidence and severity of EAE, which closely paralleled the inhibition of MOG 35-55 -specific IL-17 production. Importantly, PSA inhibited the transcription of IL-17 mRNA and RORγt. Further studies examining intracellular staining and adoptive transfer EAE validated the direct suppressive effect of PSA on Th17 cells. In vitro studies also showed that PSA significantly inhibited the differentiation of Th17 cells from murine purified CD4 + T cells in a dose-dependent manner. Conclusion: PSA ameliorated EAE by suppressing IL-17 production and inhibited the differentiation of Th17 cells in vitro. Our results provide new insight into the potential mechanisms underlying the immunosuppressive and anti-inflammatory effects of PSA.

show abstract

A non-peptide CCR5 antagonist inhibits collagen-induced arthritis by modulating T cell migration without affecting anti-collagen T cell responses

Cited by 115 publications

References 41 publications

Negative association between the chemokine receptor CCR5-Δ32 polymorphism and rheumatoid arthritis: a meta-analysis

Negative association between the chemokine receptor CCR5-Δ32 polymorphism and rheumatoid arthritis: a meta-analysis

Pharmacological Characterization of CXC Chemokine Receptor 3 Ligands and a Small Molecule Antagonist

Periplocoside A prevents experimental autoimmune encephalomyelitis by suppressing IL-17 production and inhibits differentiation of Th17 cells

Contact Info

Product

Resources

About