PMID: 31376257Aug 4, 2019Paper

IL-17A upregulates P-glycoprotein expression in peripheral blood lymphocytes of patients with rheumatoid arthritis through TAK1

Clinical and Experimental Rheumatology
Zhaohua LiCaihong Wang

Abstract

P-glycoprotein (P-gp) mediated drug efflux is the most essential mechanism of multi-drug resistance (MDR) in rheumatoid arthritis (RA). The study was undertaken to clarify the mechanism whereby IL-17 regulate the P-gp efflux function in peripheral blood lymphocytes of patients with RA. Lymphocytes from RA patients and healthy individuals were cultured with IL-17A (0, 10, 100 ng/ml), IL-17A+(5Z)-7-Oxozeaenol (TAK1 inhibitor), and IL-17A+PD98059 (ERK inhibitor), respectively. 24h later, the level of P-gp mRNA expression in peripheral blood lymphocytes was detected by RT-PCR. Meanwhile, the efflux potential of P-gp was assessed by flow cytometry using the fluorescent dye Rhodamine 123, a substrate of P-gp. In order to confirm whether the inhibitors had worked, ERK1/2 and p65, as well as their phosphorylation were detected utilising Western blot analysis. With the exception of the expression of P-gp mRNA between control and IL-17A group, the mRNA expression, as well as the function of P-gp in the different group of healthy individuals was similar, and there was no significant difference (p>0.05). However, as for the RA patients, increased expressions of P-gp mRNA and efflux function were detected in IL-17A group compared with contr...Continue Reading

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