[Study on Down-regulation of Interleukin-1β Secretion by Inhibiting ABCC1/MRP1 Transporter]

Abstract

Objective: To screen interleukin (IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.

Methods: THP-1 cell line was differentiated to obtain human THP-1-derived macrophages, and the primary macrophages were obtained from human peripheral blood. FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice. The macrophages in abdominal cavity and bone marrow of mice were cultivated. The cells were treated with ABCC1/MRP1, ABCG2/BCRP, ABCB1/P-gp, OATP1B1, and MATE transporter inhibitors, then stimulated by lipopolysaccharide and adenosine triphosphate. The secretion level of IL-1β was detected by ELISA, Western blot, and immunofluorescence.

Results: After inhibiting ABCC1/MRP1 transporter, the secretion of IL-1β decreased significantly, while inhibition of the other 4 transporters had no effect. In animal experiment, the level of IL-1β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group (P < 0.05).

Conclusion: ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway, which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Keywords: ABCC1; MRP1; macrophage; interleukin-1β; cytokine release syndrome.