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Consequently, THP-1 cells were differentiated (200 nM phorbol 12-myristate 13-acetate; 72\u00a0h) and polarized to M1 (50 ng\/mL lipopolysaccharide, 20 ng\/mL interferon-gamma; 48\u00a0h) or M2 (20 ng\/mL interleukin-4, interleukin-13; 48\u00a0h) macrophages. Then, quantitative polymerase-chain reaction array-based transcriptional analysis, flow cytometry, and ultra-performance liquid chromatography coupled to tandem mass spectrometry were used to evaluate the impact of differentiation and polarization on the expression levels of 84 drug transporter genes, the efflux activity of P-gp, and the cellular rifampicin uptake kinetics.\n                    <jats:italic>ABCB1<\/jats:italic>\n                    was enhanced 166-fold during M1 polarization and 55-fold during M2 polarization. P-gp efflux activity in M2 cells was 1.55-fold higher than in M1 cells (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). Rifampicin uptake into M2 cells was lower than into M1 cells after 2\u00a0h (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01) or 4\u00a0h exposure (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.06) to 0.05 \u00b5M rifampicin. Together, when compared to M1 macrophages, M2 cells exhibit a considerably altered fingerprint of drug transporter expression levels, including an enhanced expression and activity of P-gp, being accompanied by lowered rifampicin uptake.\n                  <\/jats:p>","DOI":"10.1007\/s00204-025-04270-2","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T11:11:54Z","timestamp":1767957114000},"page":"1377-1389","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["THP-1-derived polarized macrophages differ by drug transporter transcriptomics, P-glycoprotein activity and rifampicin uptake kinetics"],"prefix":"10.1007","volume":"100","author":[{"given":"Katharina","family":"Hamburg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Bay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Burhenne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C.","family":"Stingl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-9242","authenticated-orcid":false,"given":"Dirk","family":"Theile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"4270_CR1","first-page":"164","volume":"84","author":"DO Adams","year":"1976","unstructured":"Adams DO (1976) The granulomatous inflammatory response. 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