CCR5 is involved in resolution of inflammation in proteoglycan-induced arthritis.

Abstract

OBJECTIVE:

CCR5 and its ligands (CCL3, CCL4, and CCL5) may play a role in inflammatory cell recruitment into the joint. However, it was recently reported that CCR5 on T cells and neutrophils acts as a decoy receptor for CCL3 and CCL5 to assist in the resolution of inflammation. The aim of this study was to determine whether CCR5 functions as a proinflammatory or antiinflammatory mediator in arthritis, by examining the role of CCR5 in proteoglycan (PG)-induced arthritis (PGIA).

METHODS:

Arthritis was induced by immunizing wild-type (WT) and CCR5-deficient (CCR5(-/-)) BALB/c mice with human PG in adjuvant. The onset and severity of PGIA were monitored over time. Met-RANTES was used to block CCR5 in vivo. Arthritis was transferred to SCID mice, using spleen cells from arthritic WT and CCR5(-/-) mice. The expression of cytokines and chemokines was measured by enzyme-linked immunosorbent assay.

RESULTS:

In CCR5(-/-) mice and WT mice treated with the CCR5 inhibitor Met-RANTES, exacerbated arthritis developed late in the disease course. The increase in arthritis severity in CCR5(-/-) mice correlated with elevated serum levels of CCL5. However, exacerbated arthritis was not intrinsic to the CCR5(-/-) lymphoid cells, because the arthritis that developed in SCID mouse recipients was similar to that in WT and CCR5(-/-) mice. CCR5 expression in the SCID mouse was sufficient to clear CCL5, because serum levels of CCL5 were the same in SCID mouse recipients receiving cells from either WT or CCR5(-/-) mice.

CONCLUSION:

These data demonstrate that CCR5 is a key player in controlling the resolution of inflammation in experimental arthritis.

• Authors: Paul D Doodes, Yanxia Cao, Keith M Hamel, Yumei Wang, Rachel L Rodeghero, Tamas Kobezda, Alison Finnegan
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 60 Issue 10 Pg. 2945-53 (Oct 2009) ISSN: 0004-3591 [Print] United States
• PMID: 19790057 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Ccl5 protein, mouse
• Chemokine CCL5
• Proteoglycans
• RANTES, Met-
• Receptors, CCR5

Topics

• Animals
• Arthritis, Experimental (chemically induced, metabolism, pathology)
• Cell Transplantation
• Chemokine CCL5 (metabolism, pharmacology)
• Disease Models, Animal
• Female
• Inflammation (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Mice, SCID
• Proteoglycans (adverse effects)
• Receptors, CCR5 (drug effects, genetics, metabolism)
• Spleen (cytology, transplantation)
• Synovial Fluid (metabolism)
• T-Lymphocytes (metabolism, pathology)