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


CONCLUSIONS
These data demonstrate that CCR5 is a key player in controlling the resolution of inflammation in experimental arthritis.
Rush University Medical Center, Chicago, Illinois 60612, USA.
Paul D
PD
Doodes
Yanxia
Y
Cao
Keith M
KM
Hamel
Yumei
Y
Wang
Rachel L
RL
Rodeghero
Tamas
T
Kobezda
Alison
A
Finnegan
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D017690:Cell Transplantation; D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D011509:Proteoglycans / Q000009:adverse effects*; D019713:Receptors, CCR5 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D013582:Synovial Fluid / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D011509:Proteoglycans; C108335:RANTES, Met-; D019713:Receptors, CCR5