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Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis

CXCL12 (stromal cell-derived factor 1) is a unique biological ligand for the chemokine receptor CXCR4. We previously reported that treatment with a specific CXCR4 antagonist, AMD3100, exerts a beneficial effect on the development of collagen-induced arthritis (CIA) in the highly susceptible IFN-γ re...

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Autores principales: De Klerck, Bert, Geboes, Lies, Hatse, Sigrid, Kelchtermans, Hilde, Meyvis, Yves, Vermeire, Kurt, Bridger, Gary, Billiau, Alfons, Schols, Dominique, Matthys, Patrick
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297565/
https://www.ncbi.nlm.nih.gov/pubmed/16277673
http://dx.doi.org/10.1186/ar1806
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author De Klerck, Bert
Geboes, Lies
Hatse, Sigrid
Kelchtermans, Hilde
Meyvis, Yves
Vermeire, Kurt
Bridger, Gary
Billiau, Alfons
Schols, Dominique
Matthys, Patrick
author_facet De Klerck, Bert
Geboes, Lies
Hatse, Sigrid
Kelchtermans, Hilde
Meyvis, Yves
Vermeire, Kurt
Bridger, Gary
Billiau, Alfons
Schols, Dominique
Matthys, Patrick
author_sort De Klerck, Bert
collection PubMed
description CXCL12 (stromal cell-derived factor 1) is a unique biological ligand for the chemokine receptor CXCR4. We previously reported that treatment with a specific CXCR4 antagonist, AMD3100, exerts a beneficial effect on the development of collagen-induced arthritis (CIA) in the highly susceptible IFN-γ receptor-deficient (IFN-γR KO) mouse. We concluded that CXCL12 plays a central role in the pathogenesis of CIA in IFN-γR KO mice by promoting delayed type hypersensitivity against the auto-antigen and by interfering with chemotaxis of CXCR4(+ )cells to the inflamed joints. Here, we investigated whether AMD3100 can likewise inhibit CIA in wild-type mice and analysed the underlying mechanism. Parenteral treatment with the drug at the time of onset of arthritis reduced disease incidence and modestly inhibited severity in affected mice. This beneficial effect was associated with reduced serum concentrations of IL-6. AMD3100 did not affect anti-collagen type II antibodies and, in contrast with its action in IFN-γR KO mice, did not inhibit the delayed type hypersensitivity response against collagen type II, suggesting that the beneficial effect cannot be explained by inhibition of humoral or cellular autoimmune responses. AMD3100 inhibited the in vitro chemotactic effect of CXCL12 on splenocytes, as well as in vivo leukocyte infiltration in CXCL12-containing subcutaneous air pouches. We also demonstrate that, in addition to its effect on cell infiltration, CXCL12 potentiates receptor activator of NF-κB ligand-induced osteoclast differentiation from splenocytes and increases the calcium phosphate-resorbing capacity of these osteoclasts, both processes being potently counteracted by AMD3100. Our observations indicate that CXCL12 acts as a pro-inflammatory factor in the pathogenesis of autoimmune arthritis by attracting inflammatory cells to joints and by stimulating the differentiation and activation of osteoclasts.
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spelling pubmed-12975652005-12-01 Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis De Klerck, Bert Geboes, Lies Hatse, Sigrid Kelchtermans, Hilde Meyvis, Yves Vermeire, Kurt Bridger, Gary Billiau, Alfons Schols, Dominique Matthys, Patrick Arthritis Res Ther Research Article CXCL12 (stromal cell-derived factor 1) is a unique biological ligand for the chemokine receptor CXCR4. We previously reported that treatment with a specific CXCR4 antagonist, AMD3100, exerts a beneficial effect on the development of collagen-induced arthritis (CIA) in the highly susceptible IFN-γ receptor-deficient (IFN-γR KO) mouse. We concluded that CXCL12 plays a central role in the pathogenesis of CIA in IFN-γR KO mice by promoting delayed type hypersensitivity against the auto-antigen and by interfering with chemotaxis of CXCR4(+ )cells to the inflamed joints. Here, we investigated whether AMD3100 can likewise inhibit CIA in wild-type mice and analysed the underlying mechanism. Parenteral treatment with the drug at the time of onset of arthritis reduced disease incidence and modestly inhibited severity in affected mice. This beneficial effect was associated with reduced serum concentrations of IL-6. AMD3100 did not affect anti-collagen type II antibodies and, in contrast with its action in IFN-γR KO mice, did not inhibit the delayed type hypersensitivity response against collagen type II, suggesting that the beneficial effect cannot be explained by inhibition of humoral or cellular autoimmune responses. AMD3100 inhibited the in vitro chemotactic effect of CXCL12 on splenocytes, as well as in vivo leukocyte infiltration in CXCL12-containing subcutaneous air pouches. We also demonstrate that, in addition to its effect on cell infiltration, CXCL12 potentiates receptor activator of NF-κB ligand-induced osteoclast differentiation from splenocytes and increases the calcium phosphate-resorbing capacity of these osteoclasts, both processes being potently counteracted by AMD3100. Our observations indicate that CXCL12 acts as a pro-inflammatory factor in the pathogenesis of autoimmune arthritis by attracting inflammatory cells to joints and by stimulating the differentiation and activation of osteoclasts. BioMed Central 2005 2005-08-25 /pmc/articles/PMC1297565/ /pubmed/16277673 http://dx.doi.org/10.1186/ar1806 Text en Copyright © 2005 De Klerck et al.; licensee BioMed Central Ltd.
spellingShingle Research Article
De Klerck, Bert
Geboes, Lies
Hatse, Sigrid
Kelchtermans, Hilde
Meyvis, Yves
Vermeire, Kurt
Bridger, Gary
Billiau, Alfons
Schols, Dominique
Matthys, Patrick
Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis
title Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis
title_full Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis
title_fullStr Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis
title_full_unstemmed Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis
title_short Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis
title_sort pro-inflammatory properties of stromal cell-derived factor-1 (cxcl12) in collagen-induced arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297565/
https://www.ncbi.nlm.nih.gov/pubmed/16277673
http://dx.doi.org/10.1186/ar1806
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