Periarticular tissue levels of cytokine- and endothelin-1-like immunoreactivity during the course of antigen-induced arthritis in the rat

Andersson, Sven; Lexmuller, Kristina; Alving, Kjell; Ekström, Gunilla

doi:10.1007/s000110050492

Cited by 11 publications

(9 citation statements)

References 20 publications

(29 reference statements)

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“…Cytokine profile during chronic AIA IL-1 was the only cytokine to remain significantly elevated in the joints during chronic AIA, similarly to findings in other arthritis models [40,45]. The temporal coincidence with the progression of joint destruction, starting in the early chronic phase (see Figure 1C), is compatible with a central importance of this cytokine for the destruction of cartilage and bone in experimental arthritis [46,47].…”

Section: Cytokine Profile During Acute Aiasupporting

confidence: 68%

Systemic Macrophage Activation in Locally-induced Experimental Arthritis

Simon

Surber

Kleinstäuber

et al. 2001

Journal of Autoimmunity

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Section: Cytokine Profile During Acute Aiasupporting

confidence: 68%

Systemic Macrophage Activation in Locally-induced Experimental Arthritis

Simon

Surber

Kleinstäuber

et al. 2001

Journal of Autoimmunity

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“…The acute joint inflammation in this model resembles in several respects the corresponding reaction in RA patients. [40][41][42][43] AIA is ameliorated by MTX when administrated in a similar way as in the clinic (weekly oral dosing). The exact mechanism of action is not established, but since folate supplementation in excess can override the antiarthritic effect of MTX, it is concluded that folate antagonism is essential.…”

Section: N-[4-[(24-diaminoquinazolin-6-yl)methoxycarbonyl]benzoyl]-l-...mentioning

confidence: 99%

Computational Predictions of Binding Affinities to Dihydrofolate Reductase: Synthesis and Biological Evaluation of Methotrexate Analogues

et al. 2000

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The relative binding affinities to human dihydrofolate reductase of four new potential antifolates, containing ester linkages between the two aromatic systems, were estimated by free energy perturbation simulations. The ester analogue, predicted to exhibit the highest binding affinity to human dihydrofolate reductase, and a reference ester (more structurally related to methotrexate) were synthesized. As deduced from the measured IC(50) values, the calculated ranking of the ligands was correct although a greater difference in affinity was indicated by the experimental measurements. Among the new antifolates the most potent inhibitor exhibited a similar pharmacokinetic profile to methotrexate but lacked activity in a complex antiarthritic model in rat in vivo.

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“…In addition, sera samples from RA patients with systemic involvement showed higher ET-1 concentrations than those from RA patients without systemic inflammation [14]. Increased ET-1 levels were also found in periarticular tissue from rats submitted to antigen-induced arthritis [17]. Although several of the proinflammatory effects of ET-1 are well-described, its correlation with RA joint inflammation remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Endothelins modulate inflammatory reaction in zymosan-induced arthritis: participation of LTB4, TNF-α, and CXCL-1

Conte

Barja‐Fidalgo

Verri

et al. 2008

Journal of Leukocyte Biology

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Endothelins (ETs) are involved in inflammatory events, including pain, fever, edema, and cell migration. ET-1 levels are increased in plasma and synovial membrane of rheumatoid arthritis (RA) patients, but the evidence that ETs participate in RA physiopathology is limited. The present study investigated the involvement of ETs in neutrophil accumulation and edema formation in the murine model of zymosan-induced arthritis. Intra-articular (i.a.) administration of selective ET(A) or ET(B) receptor antagonists (BQ-123 and BQ-788, respectively; 15 pmol/cavity) prior to i.a. zymosan injection (500 microg/cavity) markedly reduced knee-joint edema formation and neutrophil influx to the synovial cavity 6 h and 24 h after stimulation. Histological analysis showed that ET(A) or ET(B) receptor blockade suppressed zymosan-induced neutrophil accumulation in articular tissue at 6 h. Likewise, dual blockade of ET(A)/ET(B) with bosentan (10 mg/kg, i.v.) also reduced edema formation and neutrophil counts 6 h after zymosan stimulation. Pretreatment with BQ-123 or BQ-788 (i.a.; 15 pmol/cavity) also decreased zymosan-induced TNF-alpha production within 6 h, keratinocyte-derived chemokine/CXCL1 production within 24 h, and leukotriene B(4) at both time-points. Consistent with the demonstration that ET receptor antagonists inhibit zymosan-induced inflammation, i.a. injection of ET-1 (1-30 pmol/cavity) or sarafotoxin S6c (0.1-30 pmol/cavity) also triggered edema formation and neutrophil accumulation within 6 h. Moreover, knee-joint synovial tissue expressed ET(A) and ET(B) receptors. These findings suggest that endogenous ETs contribute to knee-joint inflammation, acting through ET(A) and ET(B) receptors and modulating edema formation, neutrophil recruitment, and production of inflammatory mediators.

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Periarticular tissue levels of cytokine- and endothelin-1-like immunoreactivity during the course of antigen-induced arthritis in the rat

Abstract: Transient waves of different mediators appear during the course of the arthritis. This indicates the presence of active downregulatory mechanisms. Here the model could differ from human rheumatoid arthritis.

Cited by 11 publications

References 20 publications

Systemic Macrophage Activation in Locally-induced Experimental Arthritis

Systemic Macrophage Activation in Locally-induced Experimental Arthritis

Computational Predictions of Binding Affinities to Dihydrofolate Reductase: Synthesis and Biological Evaluation of Methotrexate Analogues

Endothelins modulate inflammatory reaction in zymosan-induced arthritis: participation of LTB4, TNF-α, and CXCL-1

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