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

Plater-Zyberk, C; Hoogewerf, Arlene J.; Proudfoot, Amanda E. I.; Power, Christine; Wells, Timothy N.C.

doi:10.1016/s0165-2478(97)00075-8

Cited by 209 publications

(128 citation statements)

References 28 publications

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“…Chemokine antagonists have similarly shown promise. For instance, a 67-amino acid sequence of MCP-1 that specifically antagonizes MCP-1 abrogated arthritis in MRL-lpr autoimmune mice, and an antagonist of RANTES ameliorated CIA in mice (47)(48)(49). IL-1 receptor antagonist protein, a naturally produced specific antagonist of IL-1␤, has consistently shown potent antiinflammatory properties in animal models of inflammation (50)(51)(52) and is used in the treatment of RA (53)(54)(55)(56)(57)(58).…”

Section: Discussionmentioning

confidence: 99%

CXCL16‐mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway

Ruth¹,

Haas²,

Park³

et al. 2006

Arthritis & Rheumatism

107

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Objective. Rheumatoid arthritis (RA) is characterized by profound mononuclear cell (MNC) recruitment into synovial tissue (ST), thought to be due in part to tumor necrosis factor ␣ (TNF␣), a therapeutic target for RA. Although chemokines may also be involved, the mechanisms remain unclear. We undertook this study to examine the participation of CXCL16, a novel chemokine, in recruitment of MNCs to RA ST in vivo and to determine the signal transduction pathways mediating this process. Conclusion. Taken together, these results point to a unique role for CXCL16 as a premier MNC recruiter in RA and suggest additional therapeutic possibilities, targeting CXCL16, its receptor, or its signaling pathways.

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Section: Discussionmentioning

confidence: 99%

CXCL16‐mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway

Ruth¹,

Haas²,

Park³

et al. 2006

Arthritis & Rheumatism

107

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“…Chemokines and their receptors play a critical role in the regulation of leukocyte recruitment during RA, as evidenced by the detection of these factors in RA SF and inhibition studies in animal models (5,6,19). It has been suggested that chemokine receptors may work in concert or succession to successfully recruit cells to sites of inflammation (20).…”

Section: Discussionmentioning

confidence: 99%

Up‐regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis

Galligan¹,

Matsuyama²,

Matsukawa³

et al. 2004

Arthritis & Rheumatism

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Objective. Rheumatoid arthritis (RA) is a chronic inflammatory condition characterized by a cellular influx and destruction of the joint architecture. Chemokines characteristically regulate leukocyte recruitment and activation. Chemokine (CC motif) receptor-like 2 (CCRL2) is an orphan receptor with homology to other CC chemokine receptors. We undertook this study to examine CCRL2 expression in RA, cytokine regulation of expression, and the source of a putative ligand in an attempt to determine the role of this receptor during inflammation.Methods. Expression of CCRL2 on joint-infiltrating leukocytes was examined by immunocytochemistry. In vitro studies evaluated CCRL2 expression in primary neutrophils using Northern and Western blotting and reverse transcriptase-polymerase chain reaction. HEK 293 cells expressing two splice variants of CCRL2 (HEK/CCRL2A or HEK/CCRL2B) were generated with a retroviral expression system, and their migration in response to fractions of synovial fluid (SF) from RA patients was examined using a 48-well chamber.Results. CCRL2 expression was observed on all infiltrating neutrophils and on some macrophages obtained from the SF of 5 RA patients. In vitro studies of primary neutrophils revealed that CCRL2 messenger RNA (mRNA) was rapidly up-regulated following stimulation with lipopolysaccharide (1 g/ml) or tumor necrosis factor (5 ng/ml). The mRNA for both CCRL2A and CCRL2B were expressed in cytokinestimulated neutrophils. Cells expressing either of these splice variants migrated in response to a fraction of RA SF.Conclusion. CCRL2 expression is up-regulated on synovial neutrophils of RA patients. Inflammatory products present in the SF activate this receptor, indicating that CCRL2 is a functional receptor that may be involved in the pathogenesis of RA.

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“…After all, it probably augments a pre-existing response that, to begin with, is not sufficient to entirely suppress the development of an autoimmune condition. Interestingly, targeting the function of a single proinflammatory mediator suppresses a disease regulated by various cytokines and chemokines (13,(43)(44)(45)(46)(47)(48)(49)(50). These results are very surprising since different chemokines bind and activate common chemokine receptors.…”

Section: Discussionmentioning

confidence: 99%

Targeting the Function of IFN-γ-Inducible Protein 10 Suppresses Ongoing Adjuvant Arthritis

Salomon¹,

Netzer²,

Wildbaum³

et al. 2002

The Journal of Immunology

121

115

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IFN-γ-inducible protein 10 (IP-10) is a CXC chemokine that is thought to manifest a proinflammatory role because it stimulates the directional migration of activated T cells, particularly Th1 cells. It is an open question whether this chemokine is also directly involved in T cell polarization. We show here that during the course of adjuvant-induced arthritis the immune system mounts a notable Ab titer against self-IP-10. Upon the administration of naked DNA encoding IP-10, this titer rapidly accelerates to provide protective immunity. Self-specific Ab to IP-10 developed in protected animals, as well as neutralizing Ab to IP-10 that we have generated in rabbits, could inhibit leukocyte migration, alter the in vivo and in vitro Th1/Th2 balance toward low IFN-γ, low TNF-α, high IL-4-producing T cells, and adoptively transfer disease suppression. This not only demonstrates the pivotal role of this chemokine in T cell polarization during experimentally induced arthritis but also suggests a practical way to interfere in the regulation of disease to provide protective immunity. From the basic science perspective, this study challenges the paradigm of in vivo redundancy. After all, we did not neutralize the activity of other chemokines that bind CXCR3 (i.e., macrophage-induced gene and IFN-inducible T cell α chemoattractant) and yet significantly blocked not only adjuvant-induced arthritis but also the in vivo competence to mount delayed-type hypersensitivity.

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

Cited by 209 publications

References 28 publications

CXCL16‐mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway

CXCL16‐mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway

Up‐regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis

Targeting the Function of IFN-γ-Inducible Protein 10 Suppresses Ongoing Adjuvant Arthritis

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