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In comparison with the conventional lipopolysaccharide (LPS)\u2013stimulated RAW264.7 murine macrophage model, the HaCaT\u2010based system demonstrated enhanced sensitivity, detecting significant cytokine inhibition at concentrations up to 1000\u2010fold lower for certain actives. The model reliably distinguished established anti\u2010inflammatory agents (ectoine, troxerutin, and dipotassium glycyrrhizinate) from non\u2010active controls (glycerin, butanediol, and propylene glycol) through the suppression of interleukin\u20106 (IL\u20106). Notably, the HaCaT model also identified a potential pro\u2010inflammatory shift at high concentrations of some active ingredients\u2014an effect not observed in the RAW264.7 system. Multi\u2010laboratory verification using the novel cosmetic ingredient \u03b2\u2010nicotinamide mononucleotide (NMN) confirmed both the anti\u2010inflammatory activity of NMN and the high reproducibility of the assay. These results support the TNF\u2010\u03b1\u2010HaCaT model as a sensitive, human\u2010relevant, and reproducible alternative for screening cosmetic ingredients, contributing to the growing toolbox of nonanimal methods for safety and efficacy assessment.<\/jats:p>","DOI":"10.1002\/jat.70120","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T14:45:21Z","timestamp":1772981121000},"page":"3394-3402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced Sensitivity and Human Relevance: a TNF\u2010\u03b1\u2010Induced HaCaT Keratinocyte Model for Screening Anti\u2010Inflammatory Cosmetic Materials"],"prefix":"10.1002","volume":"46","author":[{"given":"Weizuo","family":"Liao","sequence":"first","affiliation":[{"name":"Food Safety and Health Research Center, NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for Contaminants 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