{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:44:41Z","timestamp":1788389081776,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":195,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Paraquat (PQ) can cause multiorgan failure including acute kidney injury (AKI). Our prior study showed that Toll\u2010interacting protein (TOLLIP) protected against PQ\u2010induced acute lung injury. However, the role of TOLLIP in PQ\u2010induced AKI remains undefined. This study was aimed at understanding the role and mechanism of TOLLIP in AKI. Six\u2010eight\u2010week\u2010old male Wistar rats were intraperitoneally injected with 25\u2009mg\/kg PQ to induce AKI for 24\u2009h <jats:italic>in vivo<\/jats:italic>. HK\u20102 cells were treated with 300\u2009<jats:italic>\u03bc<\/jats:italic>M PQ for 24\u2009h to induce cellular injury <jats:italic>in vitro<\/jats:italic> or 300\u2009<jats:italic>\u03bc<\/jats:italic>M PQ and 5\u2009<jats:italic>\u03bc<\/jats:italic>M nuclear factor\u2010<jats:italic>\u03ba<\/jats:italic>B (NF\u2010<jats:italic>\u03ba<\/jats:italic>B) inhibitor BAY11\u20107082 for 24\u2009h. Rats were infected with adenovirus carrying TOLLIP shRNA via tail vein injection and HK\u20102 cells with adenovirus carrying TOLLIP shRNA or TOLLIP 48\u2009h before PQ exposure. Results showed that TOLLIP and Toll\u2010like receptor 2\/4 (TLR2\/4) expressions were boosted in the kidney after PQ intoxication. The toxic effect of PQ on the kidney and HK\u20102 cells was exacerbated by TOLLIP knockdown, as evidenced by aggravated glomerulus and tubule injury, inflammatory infiltration, and cell apoptosis in the kidney and increased loss of cell viability and apoptotic cells in HK\u20102 cells. TOLLIP knockdown also enhanced PQ\u2010induced NLR family pyrin domain\u2010containing 3 (NLRP3) inflammasome activation <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> and TLR2\/4\u2010NF\u2010<jats:italic>\u03ba<\/jats:italic>B signaling <jats:italic>in vitro<\/jats:italic>, reflected by increased contents of proinflammatory cytokines and expressions of NLRP3 inflammasome\u2010related proteins in the kidney and HK\u20102 cells and expressions of TLR2, TLR4, and nuclear NF\u2010<jats:italic>\u03ba<\/jats:italic>B p65 in HK\u20102 cells. However, TOLLIP overexpression inhibited PQ\u2010induced loss of cell viability, cell apoptosis, NLRP3 inflammasome activation, and TLR2\/4\u2010NF\u2010<jats:italic>\u03ba<\/jats:italic>B signaling <jats:italic>in vitro<\/jats:italic>. Additionally, BAY11\u20107082 abolished TOLLIP knockdown\u2010induced NLRP3 inflammasome activation <jats:italic>in vitro<\/jats:italic>, indicating that TOLLIP protected against NLRP3 inflammasome activation in PQ\u2010induced AKI through inhibiting TLR2\/4\u2010NF\u2010<jats:italic>\u03ba<\/jats:italic>B signaling. This study highlights the importance of TOLLIP in AKI after PQ intoxication.<\/jats:p>","DOI":"10.1155\/2021\/5571272","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T20:20:10Z","timestamp":1626380410000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Overexpression of TOLLIP Protects against Acute Kidney Injury after Paraquat Intoxication through Inhibiting NLRP3 Inflammasome Activation Modulated by Toll\u2010Like Receptor 2\/4 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