THU0024 INHIBITION OF CELL PROLIFERATION AND PROMOTION OF INTERLEUKIN-8 PRODUCTION BY T-614 IN CULTURED HUMAN AORTIC ADVENTITIAL FIBROBLASTS

Background Takayasu’s arteritis (TA) is an inflammatory fibrosing arteritis that affects predominantly the aorta and its main branches. Recently, growing evidence supports that adventitial fibroblasts play an essential role in vascular inflammation [1].Tumor necrosis factor-α (TNF-α) can reportedly induce inflammation of vascular adventitial fibroblasts[2]. T-614(iguratimod), a novel disease-modifying antirheumatic drug, has been widely used in rheumatoid arthritis in China and Japan [3]. However, the effect and mechanism of T-614 on TA have received little attention. Objectives We report the effects of T-614 on cell proliferation and interleukin-8 (IL-8) production in cultured human aortic adventitial fibroblasts (HAAF), and explored its possible effect on the treatment of TA. Methods HAAF were cultured with 0, 5, 50, 100, or 250 μg/ml T-614 in the absence or presence of 10 ng/ml TNF-α in vitro. Cell viability of HAAF was determined by a modified MTT assay. Supernatant IL-8 level was measured by enzyme linked immunosorbent assay. Results (1)After subculture, HAAF were polygonal or spindle-shaped under the microscope (Figure 1A, B).(2)In the presence of TNF-α, compared with the contrast group, cell viability of HAAF significantly decreased in 50, 100, and 250 μg/ml T-614 treatment groups (OD value: P TNF-α, tumor necrosis factor-α; HAAF, human aortic adventitial fibroblasts. Data are shown as mean ± SD of 3 independent experiments, each in triplicate. ***P Conclusion T-614 can inhibit the proliferation of HAAF and promote IL-8 production; therefore, it may provide a new immunotherapeutic intervention for TA. References [1] Maiellaro, K. and W.R. Taylor, The role of the adventitia in vascular inflammation. Cardiovasc Res, 2007. 75(4): p. 640-8. [2] He, Y., et al., SIRT6 inhibits TNF-alpha-induced inflammation of vascular adventitial fibroblasts through ROS and Akt signaling pathway. Exp Cell Res, 2017. 357(1): p. 88-97. [3] Wei, Y., et al., Inhibitory Effect of a Novel Antirheumatic Drug T-614 on the IL-6-Induced RANKL/OPG, IL-17, and MMP-3 Expression in Synovial Fibroblasts from Rheumatoid Arthritis Patients. Biomed Res Int, 2015. 2015: p. 214683. Acknowledgement Funding: This project was supported by grants from China International Medical Foundation(Z-2014-06-2-1636).The sponsors had no role in the study design, data collection and analysis, decision to publish, or preparation. Disclosure of Interests None declared