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Modulation of the response of rheumatoid arthritis synovial fibroblasts to proinflammatory stimulants with cyclic tensile strain.

Abstract：

:Although physical therapy has been shown to be an effective method for treatment of rheumatoid arthritis, a thorough investigation on the impact of mechanical signals upon the complex cytokine network associated with pathogenesis has not yet been conducted. In the current study, our research group investigated the effect of mechanical stimulation on primary and immortalized rheumatoid arthritis synovial fibroblasts (RASFs) through analysis of secreted proteins using multiplex immunoassay. Equibiaxial tensile strain was applied to 2D cultures grown on collagen-coated, flexible silicone membranes at a magnitude of 10% and a frequency of 0.5Hz using the Flexcell System. After 24h, supernatant was removed and assayed for the following cytokines: IL-1beta, IL-6, IL-8, VEGF, FGF-2, GM-CSF, MCP-1, RANTES, TNF-alpha. The results were compared to unstimulated control groups. Mechanical stimulation alone only impacted secretion of IL-8 by primary RASFs. However, in the presence of proinflammatory mediators (TNF-alpha or IL-17), application of cyclic tensile strain increased secretion of a number of proteins by both primary and immortalized RASFs, although the responses were not analogous. In contrast, MCP-1 secretion was decreased when mechanical stimulation was applied in combination with IL-17 to primary cultures. In general, the study suggests that cyclic tensile strain can be used to modulate the effects of proinflammatory stimulants on RASFs; however, given the highly variable results, more research will be necessary to identify the pathways that are implicated in mechanotransduction.

journal_name

Cytokine

journal_title

Cytokine

authors

Bader RA,Wagoner KL

doi

10.1016/j.cyto.2010.03.015

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

35-41

issue

1

eissn

1043-4666

issn

1096-0023

pii

S1043-4666(10)00089-X

journal_volume

51

pub_type

杂志文章

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