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Kupffer cells (KCs) are one of the first immune cells to contact with exotic\u2010substances in liver. Therefore, this study investigates the immunomodulatory effects and mechanisms of polyethylene glycol\u2010modified graphene oxide (GO\u2010PEG) on KCs. Initial RNA\u2010seq and KEGG pathway analyses reveal the inhibition of the TOLL\u2010like receptor, TNF\u2010\u03b1 and NOD\u2010like receptor pathways in continually stimulated KCs exposed to GO\u2010PEG. Subsequent biological experiments validate that a 48\u2010hour exposure to GO\u2010PEG alleviates LPS\u2010induced KCs immune activation, characterized by a shift in polarization from M1 to M2. The underlying mechanism involves the absorption of double\u2010stranded RNA\/single\u2010stranded RNA, inhibiting the activation of TLR3 and TLR7 in KCs. Employing a Kupffer\/AML12 cell co\u2010culture model and animal studies, it is observed that GO\u2010PEG indirectly inhibit oxidative stress, mitochondrial dysfunction, and apoptosis in AML12 cells, partially mitigating systemic inflammation and preserving liver tissue\/function. This effect is attributed to the paracrine interaction between KCs and hepatocytes. These findings suggest a meaningful and effective strategy for treating liver inflammation, particularly when combined with anti\u2010inflammatory drugs.<\/jats:p>","DOI":"10.1002\/smll.202306483","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T03:31:17Z","timestamp":1705462277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["GO\u2010PEG Represses the Progression of Liver Inflammation via Regulating the M1\/M2 Polarization of Kupffer Cells"],"prefix":"10.1002","volume":"20","author":[{"given":"Xiaomeng","family":"Ding","sequence":"first","affiliation":[{"name":"Ministry of Education Key Laboratory of Environmental Medicine Engineering School of Public Health Southeast University Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanting","family":"Pang","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory 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