Impact of rifampicin on P-glycoprotein (ABCB1) expression in M1 and M2 macrophages derived from the THP-1 monocytic cell line or peripheral blood mononuclear cells.

Rifampicin induces ABCB1 (coding for P-glycoprotein; P-gp) in enterocytes or hepatocytes, lowering drug levels and efficacy. However, there is no induction data for macrophages, the primary site of rifampicin's anti-tuberculosis action. THP-1 cells were differentiated (200 nM phorbol 12-myristate-13-acetate; 72 h) and polarized to M1 macrophages (50 ng/mL lipopolysaccharide (LPS), 20 ng/mL interferon-gamma (IFNγ); 48 h) or M2 macrophages (20 ng/mL interleukin 4 (IL-4) and interleukin 13 (IL-13) each; 48 h). Peripheral blood mononuclear cells (PBMC) from a healthy volunteer were differentiated using a commercial kit and polarized to M1 (10 ng/mL LPS and 50 ng/mL IFNγ; 72 h) or to M2 cells (20 ng/mL IL-4 and IL-13 each; 72 h). Polarized macrophages were exposed to 10 µM rifampicin for 1 week and mRNA levels of ABCB1, ABCG2 (coding for breast cancer resistance protein), and SLCO2B1 (coding for organic anion-transporting polypeptide 2B1) were evaluated by quantitative real-time polymerase chain reaction. P-gp protein levels were evaluated by Western blot analysis. Rifampicin enhanced ABCB1 in THP-1-derived M1 cells (fivefold) and M2 cells (sixfold; protein increased by 50%), but not in PBMC-derived macrophages (linear regression model). However, this effect was not significant in the three-way ANOVA, given the strong influence of macrophage polarization (M1 vs. M2) and macrophage source (THP-1 vs. PBMC). ABCG2 was enhanced twofold in THP-1-derived M2 cells (linear regression model), while SLCO2B1 remained unaffected by rifampicin. In conclusion, ABCB1 expression in macrophages differs by the cell model (THP-1 cell line vs. primary PBMC) and the polarization phenotype (M1 vs. M2). Strong rifampicin-mediated enhancements of ABCB1 were only observed in THP-1-derived M1 and M2 cells.