JN-2, a C-X-C motif chemokine receptor 3 antagonist, ameliorates arthritis progression in an animal model.
In: European journal of pharmacology, Jg. 823 (2018-03-15), S. 1-10
academicJournal
Zugriff:
Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by uncontrolled joint inflammation and destruction of bone and cartilage. Previous studies have shown that C-X-C motif chemokine 10 (CXCL10) has important roles in RA development and that blocking CXCL10 expression effectively inhibits arthritis progression in animal models. However, clinical study using anti-CXCL10 monoclonal antibody (MDX-1100) to block CXCL10 expression in patients with RA did not show significant effectiveness. Therefore, we turned our attention to C-X-C motif chemokine receptor 3 (CXCR3), which is a receptor for CXCL9, CXCL10, and CXCL11, to treat RA. In the present study, administration of JN-2, our newly developed CXCR3 antagonist, ameliorated the progression of arthritis in a collagen-induced arthritis animal model. JN-2 also inhibited CXCR3-induced cell migration and pro-inflammatory cytokine expression of bone marrow-derived macrophages and CD4 + T cells in vitro. In addition, we found that CXCL10 formed an auto-amplification loop through activation of NFκB. Furthermore, Phosphorylation of p65 at serine 536 played an important role in the auto-amplification of CXCL10. Overall, the present results demonstrated that JN-2 decreased inflammation by inhibiting CXCR3-enhanced cell migration and pro-inflammatory cytokine expression, which then ameliorated arthritis progression.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Titel: |
JN-2, a C-X-C motif chemokine receptor 3 antagonist, ameliorates arthritis progression in an animal model.
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Autor/in / Beteiligte Person: | Kim, B ; Lee, JH ; Jin, WJ ; Kim, HH ; Ha, H ; Lee, ZH |
Zeitschrift: | European journal of pharmacology, Jg. 823 (2018-03-15), S. 1-10 |
Veröffentlichung: | 2005- : Amsterdam : Elsevier Science ; <i>Original Publication</i>: Amsterdam, North Holland Pub. Co., 2018 |
Medientyp: | academicJournal |
ISSN: | 1879-0712 (electronic) |
DOI: | 10.1016/j.ejphar.2018.01.037 |
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