AB0124 IMPACT OF INFLAMMATORY CYTOKINE IL-1β ON THE EXPRESSION OF MULTIPLE DRUG RESISTANCE PROTEIN BCRP/ABCG2 IN SYNOVIOCYTES OF PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Fang Yuan Hu, Ning Yan, Jie Liang, Xiang-Cong Zhao, LI Zhao-Hua, Chong Gao, LI Xiao-Feng, Caihong Wang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis and vasospasm<sup>[1]</sup>. So far, The biggest challenge in the current field of RA treatment is the production of DMARDs multidrug resistance (MDR) and the most critical mechanism for the production of MDR is the ABC transporter family-mediated increase in target cell drug excretion, while inflammatory cytokines play an important role in its expression regulation. Our previous research have confirmed that IL-1β, IL-6 and IL-17 are involved in the regulation of P-glycoprotein (P-gp) expression in lymphocytes of RA patients. The breast cancer resistance protein (BCRP/ABCG2) is also a highly efficient efflux pump, which absorbs, distributes, and excretes drugs or exogenous substances in the body<sup>[2]</sup>. IL-1βis a cytokine involved in the whole process of RA, which can aggravate the inflammatory response. However, there is no research on the effect of IL-1β on the expression of BCRP in RA Fibroblast-like synoviocytes (FLS). <h3>Objectives</h3> To explore the effects of different concentrations of IL-1β on the expression of drug resistance proteins in FLS of RA patients at different time points. <h3>Methods</h3> Synovial tissues of untreated RA patients (n=3) were extracted by Joint surgery, FLS culture system in vitro was established and passaged to the fifth generation or so to do the experiments. FLS cells were divided into A, B, C, D four groups randomly with different treatments: Group A was the cell control group. Group B, C, D were respectively co-cultured with low (20ng/ml), middle (50ng/ml), high (100ng/ml) concentrations of IL-1β. They were cultured respectively for 24 hours, 48 hours, and 72 hours. The effect of IL-1β on the expression level of BCRP mRNA was observed at different concentrations and at different time points. <h3>Results</h3> With the prolongation of IL-1βculture, the expression of BCRP mRNA increased. Under the same concentration of IL-1β(20ng/ml or 50ng/ml), the expression of BCRP mRNA in the 72h group was higher than that in the 24h group or 48h group (P&lt;0.05). At the concentration of IL-1βof 20 ng/ml, the 48h group showed higher levels of BCRP mRNA expression than the 24h group (P&lt;0.05). The expression of BCRP mRNA increased with the increase of IL-1βconcentration. After 48h of IL-1βculture, the 100 ng/ml group showed high levels of BCRP mRNA expression compared with the 0 ng/ml group (P&lt;0.05). After 72h of IL-1βculture, compared with the 0 ng/ml group, the expression of BCRP mRNA was significantly increased in the 20 ng/ml or 50 ng/ml or 100 ng/ml group (P&lt;0.01); and the 100 ng/ml group showed high levels of BCRP mRNA expression compared with the 20 ng/ml group (P &lt; 0.05). <h3>Conclusion</h3> The expression of BCRP mRNA in FLS of RA patients has a certain concentration and time dependence of IL-1β, suggesting that IL-1β is involved in BCRP-mediated multidrug resistance, which lays a foundation for exploring its specific mechanism. <h3>References</h3> [1] Takase-Minegishi K, Horita N, Kobayashi K, et al. Diagnostic test accuracy of ultrasound for synovitis in rheumatoid arthritis: systematic review and meta-analysis[J]. Rheumatology, 2017. [2] Chen Z, Shi T, Zhang L, et al. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade[J]. Cancer Letters, 2016, 370(1): 153-164. <h3>Acknowledgement</h3> Rheumatology and laboratory staff in the Second Hospital of Shanxi Medical University <h3>Disclosure of Interests</h3> None declared