Dados do Trabalho

Title

FASCIOLA HEPATICA EXTRACT ALTERS VIABILITY, ADHESION, MIGRATION AND INVASION PROPERTIES OF SYNOVIAL FIBROBLASTS FROM PATIENTS WITH RHEUMATOID ARTHRITIS.

Background

Fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) exhibit an aggressive and invasive profile and are involved in inflammatory process of the disease, including joint degradation and bone erosion. Available treatments have been effective for induction and maintenance of disease remission, but there is no known medical/surgical cure for AR. Also, these treatments has not been successful in all patients and may cause several side effects. For that reason, therapeutic alternatives, such as helminthic therapy, are required for unresponsive patients. In this way, the Fasciola hepatica (F. hepatica) release products with immunomodulatory properties, which are capable of suppressing the Th1 immune response and the production of inflammatory cytokines. Therefore, the therapeutic potential of F. hepatica extract was evaluated in vitro on FLS from patients with RA.

Materials and methods

FLS were isolated from synovial fluid of RA patients. Cultures of FLS were exposed at different concentration of F. hepatica extract (60µg/mL, 80µg/mL and 100µg/mL) and analyzed after 24h, 48h and 72h by MTT cell viability assay. The effect of extract was also evaluated by cell adherence, wound healing and invasion, apoptosis assay, nuclear morphometric index (NMI), and TNF-α production. Statistical analysis was performed with ANOVA or T Test and p<0.05 were considered statistically significant.

Results

F. hepatica extract decreased the cell proliferation of FLS at concentration of 100µg/mL after 48h (83.8 % ± 5.0 extract vs 100.0 % ± 0.0 control; p<0.05), and at concentrations of 80µg/mL (88.4 % ± 3.0 extract vs 100.0 % ± 0.0 control; p<0.05) and 100µg/mL (89.8 % extract ± 3.8 extract vs 100.0 % ± 0.0 control; p<0. 05) after 72h, when compared with control group. Based on these results, the dose of 100µg/mL for 48h was chosen for the following tests. The treatment with F. hepatica extract showed a decreased of FLS adherence (92.0 cells ± 5.8 extract vs 116.3 cells ± 7.9 control; p<0.05), migratory potential (69.5 % ± 17.6 extract vs 100.0 % control; p<0.05) and cell invasion (80.3 % ± 3.9 extract vs 100.0 % control; p<0.05). Moreover, there was a trend of decreased TNF levels after extract treatment. However, the F. hepatica extract does not affect NMI parameters or induce cell death on FLS.

Conclusions

Taken together, our results point out F. hepatica extract as a potential strategy for AR due to their ability to reduce the aggressive and invasive profile of FLS.

Área

Rheumatoid Arthritis