Up‐regulation by tumor necrosis factor α of intercellular adhesion molecule 1 expression and function in synovial fibroblasts and its inhibition by glucocorticoids

Tessier, Philippe A.; Audette, Marie; Cattaruzzi, Paola; McColl, Shaun R.

doi:10.1002/art.1780361107

Cited by 40 publications

(1 citation statement)

References 44 publications

(3 reference statements)

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“…Accordingly to data showing the synergic effect of shear stress and TNF-α on ICAM-1 and the opposite effect of these factors on VCAM-1 [42], in our experiments ICAM-1 and VCAM-1 expression was enhanced by TNFα, with TNF-α partially rescuing the negative effect of shear stress on VCAM-1. Interestingly, TNF-α increased ICAM-1 expression also in SFbs, in line with literature showing a dose-dependent effect of TNF-α on ICAM-1 in this cell type [43].…”

Section: Discussionsupporting

confidence: 91%

Recapitulating monocyte extravasation to the synovium in an organotypic microfluidic model of the articular joint

et al. 2021

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The synovium of osteoarthritis (OA) patients can be characterized by an abnormal accumulation of macrophages originating from extravasated monocytes. Since targeting monocyte extravasation may represent a promising therapeutic strategy, our aim was to develop an organotypic microfluidic model recapitulating this process. Synovium and cartilage were modeled by hydrogel-embedded OA synovial fibroblasts and articular chondrocytes separated by a synovial fluid channel. The synovium compartment included a perfusable endothelialized channel dedicated to monocyte injection. Monocyte extravasation in response to chemokines and OA synovial fluid was quantified. The efficacy of chemokine receptor antagonists, RS-504393 (CCR2 antagonist) and Cenicriviroc (CCR2/CCR5 antagonist) in inhibiting extravasation was tested pre-incubating monocytes with the antagonists before injection. After designing and fabricating the chip, culture conditions were optimized to achieve an organotypic model including synovial fibroblasts, articular chondrocytes, and a continuous endothelial monolayer expressing intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. A significantly higher number of monocytes extravasated in response to the chemokine mix (p < 0.01) and OA synovial fluid (p < 0.01), compared to a control condition. In both cases, endothelium pre-activation enhanced monocyte extravasation. The simultaneous blocking of CCR2 and CCR5 proved to be more effective (p < 0.001) in inhibiting monocyte extravasation in response to OA synovial fluid than blocking of CCR2 only (p < 0.01). The study of extravasation in the model provided direct evidence that OA synovial fluid induces monocytes to cross the endothelium and invade the synovial compartment. The model can be exploited either to test molecules antagonizing this process or to investigate the effect of extravasated monocytes on synovium and cartilage cells.

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Section: Discussionsupporting

confidence: 91%

Recapitulating monocyte extravasation to the synovium in an organotypic microfluidic model of the articular joint

et al. 2021

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Extracellular human T cell leukemia virus type I tax protein stimulates the proliferation of human synovial cells

Aono

Fujisawa

Hasunuma

et al. 1998

Arthritis & Rheumatism

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Reduction of synovial inflammation after anti‐cd4 monoclonal antibody treatment in early rheumatoid arthritis

Tak

Lubbe

Cauli

et al. 1995

Arthritis & Rheumatism

184

138

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Objective. To study the effect of chimeric anti-CD4 monoclonal antibody (MAb) therapy on synovial inflammation, in order to interpret the clinical experience with anti-CD4 treatment.Methods. The immunohistologic features of synovial biopsy specimens before and 4 weeks after anti-CD4 MAb (cM-T412) therapy were studied in patients with rheumatoid arthritis. The patients received intravenous doses of either placebo (n = 1) or 10 mg (n = 4), 25 mg (n = 2), or 50 mg (n = 1) of cM-T412 daily for 5 consecutive days.Results. Although the patients did not experience clinical improvement, significant decreases in the number of circulating CD4+ cells, the degree of synovial inflammatory infiltration, and the mean scores for expression of adhesion molecules were found in the 7 patients 4 weeks after receiving cM-T412. The scores for infiltration with CD4+ and other inflammatory cells were particularly reduced following treatment with either 25 mg or 50 mg cM-T412. Cytokines, such as interleukin-lp and tumor necrosis factor a, could still be detected in the synovial tissue after treatment.Conclusion. The decline in the numbers of inflammatory cells and adhesion molecules in synovial tissue after CD4+ cell depletion supports the view that

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Up‐regulation by tumor necrosis factor α of intercellular adhesion molecule 1 expression and function in synovial fibroblasts and its inhibition by glucocorticoids

Abstract: These combined results provide further evidence of an important role of ICAM-1 in inflammatory synovitis, as well as a potentially novel site of antiinflammatory action of glucocorticoids.

Cited by 40 publications

References 44 publications

Recapitulating monocyte extravasation to the synovium in an organotypic microfluidic model of the articular joint

Recapitulating monocyte extravasation to the synovium in an organotypic microfluidic model of the articular joint

Extracellular human T cell leukemia virus type I tax protein stimulates the proliferation of human synovial cells

Reduction of synovial inflammation after anti‐cd4 monoclonal antibody treatment in early rheumatoid arthritis

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