Effect of a CC chemokine receptor antagonist on collagen induced arthritis in DBA/1 mice.

Abstract

Chemokines are small proteins that selectively activate and recruit leukocytes to sites of inflammation. Several of them, including the CC chemokines RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and the CXC chemokines IL-8, GRO-alpha, ENA-78 have been identified in rheumatoid synovium, implicating a potential role for these molecules in rheumatoid arthritis. We have investigated the expression patterns of CC chemokine receptors in the joints of mice with collagen-induced arthritis, a model for human rheumatoid arthritis. In addition, we have investigated the incidence and severity of arthritis in mice receiving administration of MetRANTES, a modified chemokine which is a nanomolar antagonist of certain CC chemokine receptors. The mRNA expression pattern of the chemokines and their receptors in the joints of arthritic mice was investigated using reverse transcriptase-PCR and in situ hybridization. An upregulation of the CC chemokine receptors mCCR1, mCCR2; mCCR3 and mCCR5 was found in the joints from arthritic mice, compared to control animals. In addition, injections of MetRANTES reduced the incidence of disease in a dose dependent manner. Furthermore, in MetRANTES-treated mice that did develop arthritis a significantly lower severity of disease was observed compared with control animals. Our data clearly demonstrate a role for CC chemokines and their receptors in inflammatory joint destruction and support the use of chemokine receptor antagonists as potential tools to control inflammatory diseases such as rheumatoid arthritis.

• Authors: C Plater-Zyberk, A J Hoogewerf, A E Proudfoot, C A Power, T N Wells
• Journal: Immunology letters (Immunol Lett) Vol. 57 Issue 1-3 Pg. 117-20 (Jun 01 1997) ISSN: 0165-2478 [Print] Netherlands
• PMID: 9232436 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL5
• Chemokines
• RANTES, Met-
• Receptors, Cytokine
• Collagen

Topics

• Animals
• Arthritis, Rheumatoid (chemically induced, drug therapy, metabolism)
• Chemokine CCL5 (analogs & derivatives)
• Chemokines (therapeutic use)
• Collagen
• Disease Models, Animal
• Humans
• Joints (metabolism)
• Male
• Mice
• Mice, Inbred DBA
• Receptors, Cytokine (antagonists & inhibitors, biosynthesis, genetics)
• Severity of Illness Index
• Up-Regulation