{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:02:12Z","timestamp":1785420132416,"version":"3.56.0"},"reference-count":60,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009233","name":"Majlis Amanah Rakyat","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100009233","id-type":"DOI","asserted-by":"publisher"}]},{"award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/04snr8v46","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Impaired amyloid-\u03b2 clearance at the blood\u2013brain barrier (BBB) contributes to Alzheimer\u2019s disease (AD), yet the regulation of endothelial transport processes under neuroinflammatory conditions remains incompletely understood. Here, we investigated the time-dependent effects of interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6) classical signaling directly via the membrane-bound IL-6 receptor, and IL-6 trans-signaling via the IL-6 \/soluble IL-6 receptor complex (IL-6\/sIL-6r) on ATP-binding cassette (ABC) transporter activity and expression in primary porcine brain endothelial cells (PBECs), and assessed intracellular accumulation of amyloid-\u03b2(1\u201342). Cytokine exposure did not affect PBEC viability. IL-1\u03b2 induced a robust, time-dependent increase in ABCB1 activity and expression, whereas IL-6 produced a transient enhancement that was not sustained at 72 h. In contrast, IL-6 trans-signaling elicited a delayed but sustained increase in ABCB1 function and expression. IL-1\u03b2 increased ABCG2 activity and expression at early time points, while IL-6 and IL-6\/sIL-6r had minimal effects. Notably, IL-1\u03b2 and IL-6 trans-signaling increased ABCC5 activity without detectable changes in protein expression. Cytokine-induced transporter modulation was associated with reduced intracellular amyloid-\u03b2 accumulation. Pharmacological inhibition of ABC transporters increased intracellular amyloid-\u03b2 levels, supporting a role for these transporters in endothelial amyloid-\u03b2 handling. However, as transendothelial amyloid-\u03b2 transport was not directly assessed, these findings should be interpreted as changes in intracellular amyloid-\u03b2 accumulation rather than direct evidence of altered BBB clearance. These findings demonstrate signaling- and time-dependent regulation of BBB ABC transporters and reveal distinct effects of IL-6 classical signaling and IL-6 trans-signaling on endothelial transporter regulation. Collectively, these results highlight signaling context as an important determinant of BBB transport responses under neuroinflammatory conditions.<\/jats:p>","DOI":"10.3390\/cells15141273","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:05:07Z","timestamp":1784163907000},"page":"1273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin-1\u03b2 and Interleukin-6 Signaling Differentially Regulate ABC Transporter Activity and Amyloid-\u03b2 Handling in Primary Porcine Brain Endothelial Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2563-2890","authenticated-orcid":false,"given":"Ahmad H.","family":"Razmi","sequence":"first","affiliation":[{"name":"Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey I.","family":"Penny","sequence":"additional","affiliation":[{"name":"Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1172\/JCI10498","article-title":"Clearance of Alzheimer\u2019s amyloid-\u03b21-40 peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier","volume":"106","author":"Shibata","year":"2000","journal-title":"J. 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