Literature DB >> 16905577

Differential effect of methotrexate on the increased CCR2 density on circulating CD4 T lymphocytes and monocytes in active chronic rheumatoid arthritis, with a down regulation only on monocytes in responders.

T Ellingsen1, N Hornung, B K Møller, J H Poulsen, K Stengaard-Pedersen.   

Abstract

OBJECTIVES: To evaluate the effect of orally administered methotrexate (MTX) on the density of CC chemokine receptor 2 (CCR2) and CXC chemokine receptor 3 (CXCR3) on circulating monocytes, and the coexpression of CXCR3 and CCR2 on CD4 T lymphocytes in patients with active chronic rheumatoid arthritis.
METHODS: All 34 patients with rheumatoid arthritis fulfilled the 1987 American Rheumatism Association criteria and were followed for 16 weeks after starting MTX. Peripheral blood mononuclear cells were analysed for CCR2 and CXCR3 density by three-colour flow cytometry before initiation of MTX and at week 12.
RESULTS: 22 (65%) patients were non-responders, 12 (35%) patients responded to MTX by American College of Rheumatology (ACR)20% criteria, and 8 (24%) of these patients responded by ACR50%. In patients with active rheumatoid arthritis before starting MTX, CCR2 density on circulating monocytes, CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes was increased compared with controls. During 12 weeks of MTX treatment, the CCR2 density on monocytes decreased significantly in the ACR50% group but not in the ACR20% and non-responder groups. The increased CCR2 density on CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes was unaffected by the reduction in disease activity measured in relation to MTX treatment. The percentage of both monocytes and CD4(+) CXCR3(+) and CD4+ CXCR3(-) T lymphocytes among the peripheral circulating mononuclear cells did not change during MTX treatment.
CONCLUSIONS: Active chronic rheumatoid arthritis is characterised by enhanced CCR2 density on circulating monocytes and CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes. During MTX treatment, a decrease in CCR2 density on monocytes in the ACR50% responder group was associated with decreased disease activity. The increased CCR2 density on CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes was uninfluenced by MTX and disease activity.

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Year:  2006        PMID: 16905577      PMCID: PMC1798497          DOI: 10.1136/ard.2006.054056

Source DB:  PubMed          Journal:  Ann Rheum Dis        ISSN: 0003-4967            Impact factor:   19.103


  55 in total

1.  The role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of collagen-induced arthritis in rats.

Authors:  H Ogata; M Takeya; T Yoshimura; K Takagi; K Takahashi
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2.  Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2.

Authors:  W A Kuziel; S J Morgan; T C Dawson; S Griffin; O Smithies; K Ley; N Maeda
Journal:  Proc Natl Acad Sci U S A       Date:  1997-10-28       Impact factor: 11.205

3.  The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions.

Authors:  S Qin; J B Rottman; P Myers; N Kassam; M Weinblatt; M Loetscher; A E Koch; B Moser; C R Mackay
Journal:  J Clin Invest       Date:  1998-02-15       Impact factor: 14.808

4.  CCR5 is characteristic of Th1 lymphocytes.

Authors:  P Loetscher; M Uguccioni; L Bordoli; M Baggiolini; B Moser; C Chizzolini; J M Dayer
Journal:  Nature       Date:  1998-01-22       Impact factor: 49.962

5.  Interleukin 1 (IL-1) receptor antagonist, soluble tumor necrosis factor receptors, IL-1 beta, and IL-8--markers of remission in rheumatoid arthritis during treatment with methotrexate.

Authors:  M Seitz; P Loetscher; B Dewald; H Towbin; C Rordorf; H Gallati; N J Gerber
Journal:  J Rheumatol       Date:  1996-09       Impact factor: 4.666

6.  The clinical value of the Stanford Health Assessment Questionnaire Functional Disability Index in patients with rheumatoid arthritis.

Authors:  F Wolfe; S M Kleinheksel; M A Cathey; D J Hawley; P W Spitz; J F Fries
Journal:  J Rheumatol       Date:  1988-10       Impact factor: 4.666

7.  American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis.

Authors:  D T Felson; J J Anderson; M Boers; C Bombardier; D Furst; C Goldsmith; L M Katz; R Lightfoot; H Paulus; V Strand
Journal:  Arthritis Rheum       Date:  1995-06

8.  Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.

Authors:  F Sallusto; D Lenig; C R Mackay; A Lanzavecchia
Journal:  J Exp Med       Date:  1998-03-16       Impact factor: 14.307

9.  Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.

Authors:  R Bonecchi; G Bianchi; P P Bordignon; D D'Ambrosio; R Lang; A Borsatti; S Sozzani; P Allavena; P A Gray; A Mantovani; F Sinigaglia
Journal:  J Exp Med       Date:  1998-01-05       Impact factor: 14.307

10.  An antagonist of monocyte chemoattractant protein 1 (MCP-1) inhibits arthritis in the MRL-lpr mouse model.

Authors:  J H Gong; L G Ratkay; J D Waterfield; I Clark-Lewis
Journal:  J Exp Med       Date:  1997-07-07       Impact factor: 14.307

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  5 in total

1.  Insulin-like growth factor I receptor density on CD4+T-lymphocytes from active early steroid- and DMARD-naïve rheumatoid arthritis patients is up-regulated and not influenced by 1 year of clinically effective treatment.

Authors:  Trine Bay Laurberg; Torkell Ellingsen; Jonas Thorsen; Bjarne Kuno Møller; Ib Hansen; Ulrik Tarp; Merete Lund Hetland; Kim Hørslev-Petersen; Allan Flyvbjerg; Jan Frystyk; Kristian Stengaard-Pedersen
Journal:  Rheumatol Int       Date:  2011-01-19       Impact factor: 2.631

Review 2.  Chemokine receptor antagonists: overcoming developmental hurdles.

Authors:  Richard Horuk
Journal:  Nat Rev Drug Discov       Date:  2008-12-12       Impact factor: 84.694

3.  The Situation of Chemokine Ligands and Receptors Gene Expression, Following the Oral Administration of Drug Mannuronic Acid in Rheumatoid Arthritis Patients.

Authors:  Mona Aslani; Arman Ahmadzadeh; Zahra Rezaieyazdi; Seyed S Mortazavi-Jahromi; Anis Barati; Mostafa Hosseini; Abbas Mirshafiey
Journal:  Recent Pat Inflamm Allergy Drug Discov       Date:  2020

4.  Long-term study of the impact of methotrexate on serum cytokines and lymphocyte subsets in patients with active rheumatoid arthritis: correlation with pharmacokinetic measures.

Authors:  Joel M Kremer; David A Lawrence; Robert Hamilton; Iain B McInnes
Journal:  RMD Open       Date:  2016-06-09

Review 5.  Chemokines and chemokine receptors in arthritis.

Authors:  Zoltan Szekanecz; Aniko Vegvari; Zoltan Szabo; Alisa E Koch
Journal:  Front Biosci (Schol Ed)       Date:  2010-01-01
  5 in total

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