{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:24:33Z","timestamp":1788294273636,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rosacea is a chronic inflammatory skin disease and is usually accompanied by extensive macrophage infiltration. There is growing evidence suggesting that neurotransmitter 5-hydroxytryptamine (5-HT) plays a crucial role in inflammatory reactions. However, the interaction between 5-HT and rosacea is still unclear. Here, we hypothesized that the inflammation of rosacea is partly caused by 5-HT, and we investigated the underlying mechanism. In this study, we employed a rosacea model induced by LL-37, which is usually applicated as a rosacea stimulator, to investigate the effects of 5-HT on rosacea in vitro and in vivo. In LL-37-(4 \u03bcM)-induced THP-1-derived macrophages, 5-HT (400 \u03bcM) further promoted the secretion of inflammatory cytokines and polarized macrophages towards M1 phenotype, which could promote an inflammatory response. Further research revealed that exposure to LL-37 and 5-HT (L5) selectively upregulated HTR3A mRNA expression but not HTR2A or HTR7 and induced colocalization of 5-HT with HTR3A. Notably, application of antagonist tropisetron (TPS) and siRNA of HTR3A suppressed L5-induced inflammation. Meanwhile, 5-HT (25 \u03bcg each injection a total of three times) deteriorated skin erythema, stimulated dermal inflammatory cell infiltration, and promoted the secretion of inflammatory cytokines in LL-37 (40 \u03bcL and 320 \u03bcM each injection a total of four times) induced rosacea-like mice, while these undesirable effects were reversed by using TPS. Our findings revealed that neurotransmitter 5-HT further promoted LL-37-induced rosacea-like inflammation through HTR3A. Our study highlights HTR3A as a promising therapeutic target, which warrants further in-depth investigation into its clinical applicability.<\/jats:p>","DOI":"10.3390\/ijms26073156","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T03:25:02Z","timestamp":1743391502000},"page":"3156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neurotransmitter 5-HT Further Promotes LL-37-Induced Rosacea-like Inflammation Through HTR3A"],"prefix":"10.3390","volume":"26","author":[{"given":"Haojie","family":"Ma","sequence":"first","affiliation":[{"name":"Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7485-5234","authenticated-orcid":false,"given":"Fengfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of National Health Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control, Jiangsu Institute of Parasitic Disease and Public Health Research Center of Jiangnan University, Wuxi 214064, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1820-3354","authenticated-orcid":false,"given":"Bingtian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s40257-021-00595-7","article-title":"Rosacea: New concepts in classification and treatment","volume":"22","author":"Van","year":"2021","journal-title":"Am. 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