Zusammenfassung
Fraktalkine (CX3CL1), das bisher einzige bekannte Chemokin der CX3C-Klasse, und sein Rezeptor CX3CR1 werden in der chronisch entzündeten Synovialmembran von Patienten mit rheumatoider Arthritis (RA) verstärkt exprimiert. Durch die spezifische Bindung von Fraktalkine an seinen Rezeptor werden vielfältige proinflammatorische, an der Pathogenese der RA beteiligte Reaktionen vermittelt. Im Einzelnen sind dies die Induktion der synovialen Angiogenese, die Chemotaxis, die Aktivierung von Monozyten und T-Zellen sowie die Stimulation der Proliferation und die Synthese matrixdestruierender Enzyme (Matrix-Metalloproteinasen, MMP) in synovialen Fibroblasten. Fraktalkine könnte damit langfristig eine neue molekulare Zielstruktur für die Therapie der RA darstellen.
Abstract
Fractalkine (CX3CL1), so far the only member of the CX3C class of chemokines, and its receptor, CX3CR1, are strongly expressed in the chronically inflamed synovial tissue of patients with rheumatoid arthritis (RA). Due to the specific binding of Fractalkine to its receptor, many proinflammatory reactions involved in the pathogenesis of RA are triggered. Functionally, fractalkine plays an important proinflammatory role in RA pathogenesis as characterized by induction of synovial angiogenesis, chemotaxis, activation of monocytes and T cells as well as the stimulation of proliferation and synthesis of matrix degrading enzymes (matrix metalloproteinases, MMP) in synovial fibroblasts. Fractalkine thus may represent a novel target molecule for therapeutic intervention in RA.
This is a preview of subscription content, log in via an institution to check access.
Literatur
Stievano L, Piovan E, Amadori A (2004) C and CX3C chemokines: cell sources and physiopathological implications. Crit Rev Immunol 24: 205–228
Koziolek MJ, Schmid H, Cohen C et al. (2007) Potential role of fractalkine receptor (CX3CR1) expression in human renal fibrogenesis. Kidney Int 72: 599–607
Blaschke S, Koziolek M, Schwarz A et al. (2003) Proinflammatory role of fractalkine (CX3CL1) in rheumatoid arthritis. J Rheumatol 30: 1918–1927
Matsunawa M, Isozaki T, Odai T et al. (2006) Increased serum levels of soluble fractalkine (CX3CL1) correlate with disease activity in rheumatoid vasculitis. Arthritis Rheum 45: 3408–3416
Ruth JH, Volin MV, Haines GK et al. (2001) Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis. Arthritis Rheum 44: 1568–1581
Volin MV, Woods JM, Amin MA et al. (2001) Fractalkine: a novel angiogenic chemokine in rheumatoid arthritis. Am J Pathol 159: 1521–1530
Nanki T, Imai T, Nagasaka K et al. (2002) Migration of CX3CR1-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis. Arthritis Rheum 46: 2878–2883
Volin MV, Huynh N, Klosowska K et al. (2007) Fractalkine is a novel chemoattractant for rheumatoid arthritis fibroblast-like synoviocytes signalling through MAP kinases and Akt. Arthritis Rheum 56: 2512–2522
Sawai H, Park YW, Roberson J et al. (2005) T cell costimulation by fractalkine-expressing synoviocytes in rheumatoid arthritis. Arthritis Rheum 52: 1392–1401
Sawai H, Park YW, He X et al. (2007) Fractalkine mediates T cell-dependent proliferation of synovial fibroblasts in rheumatoid arthritis. Arthritis Rheum 56: 3215–3225
Nanki T, Urasaki Y, Imai T et al. (2004) Inhibition of fractalkine ameliorates murine collagen-induced arthritis. J Immunol 173: 7010–7016
Interessenkonflikt
Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Blaschke, S., Müller, G. Fraktalkine – ein proinflammatorisches Chemokin bei rheumatoider Arthritis. Z. Rheumatol. 67, 424–428 (2008). https://doi.org/10.1007/s00393-008-0326-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00393-008-0326-1