{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T08:44:07Z","timestamp":1775119447026,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014476","name":"Pfizer Pharmaceuticals","doi-asserted-by":"publisher","award":["IIR #WI233723"],"award-info":[{"award-number":["IIR #WI233723"]}],"id":[{"id":"10.13039\/100014476","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease in which synovial fibroblasts (SF) play a key role. Baricitinib and Tofacitinib both act intracellularly, blocking the ATP-binding side of JAK proteins and thereby the downstream signalling pathway via STAT-3. Therefore, we investigated the role of organic cation transporters (OCTs) in Baricitinib and Tofacitinib cellular transport. Methods: OCT expression was analysed in SF isolated from RA and osteoarthritis (OA) patients, as well as peripheral blood mononuclear cells. The interaction of Baricitinib and Tofacitinib with OCTs was investigated using quenching experiments. The intracellular accumulation of both drugs was quantified using LC\/MS. Target inhibition for both drugs was tested using Western blot for phosphorylated JAK1 and STAT3 upon stimulation with IL-6. Results: MATE-1 expression increased in OASF compared to RASF. The other OCTs were not differentially expressed. The transport of Baricitinib was not OCT dependent. Tofacitinib; however, was exported from RASF in a MATE-1 dependent way. Tofacitinib and Baricitinib showed comparable inhibition of downstream signalling pathways. Conclusion: We observed different cellular uptake strategies for Baricitinib and Tofacitinib. Tofacitinib was exported out of healthy cells due to the increased expression of MATE1. This might make Tofacitinib the favourable drug.<\/jats:p>","DOI":"10.3390\/ijms21186632","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T09:10:09Z","timestamp":1599729009000},"page":"6632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Tofacitinib and Baricitinib Are Taken up by Different Uptake Mechanisms Determining the Efficacy of Both Drugs in RA"],"prefix":"10.3390","volume":"21","author":[{"given":"Jan","family":"Amrhein","sequence":"first","affiliation":[{"name":"Experimental Nephrology, Department of Internal Medicine D, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Drynda","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Otto-von-Guericke University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Schlatt","sequence":"additional","affiliation":[{"name":"Institute of Inorganic and Analytical Chemistry, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1774-6787","authenticated-orcid":false,"given":"Uwe","family":"Karst","sequence":"additional","affiliation":[{"name":"Institute of Inorganic and Analytical Chemistry, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph H.","family":"Lohmann","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Otto-von-Guericke University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4365-3656","authenticated-orcid":false,"given":"Giuliano","family":"Ciarimboli","sequence":"additional","affiliation":[{"name":"Experimental Nephrology, Department of Internal Medicine D, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Otto-von-Guericke University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/rheumatology\/kel065","article-title":"Synovial fibroblasts: Key players in rheumatoid arthritis","volume":"45","author":"Huber","year":"2006","journal-title":"Rheumatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e000471","DOI":"10.1136\/rmdopen-2017-000471","article-title":"Synovial fibroblasts in 2017","volume":"3","author":"Ospelt","year":"2017","journal-title":"RMD Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1002\/art.21273","article-title":"RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3","volume":"52","author":"Brentano","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1002\/art.24140","article-title":"Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: Toll-like receptor expression in early and longstanding arthritis","volume":"58","author":"Ospelt","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0174-173X(83)80040-5","article-title":"Histomorphological basis of articular cartilage destruction in rheumatoid arthritis","volume":"3","author":"Fassbender","year":"1983","journal-title":"Coll. 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