{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:38:20Z","timestamp":1792694300691,"version":"4.5.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Fund of Khon Kaen University, the National Science, Research and Innovation Fund","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Inflammation underlies numerous pathological conditions, driving the need for safe and effective anti-inflammatory agents. Anti-inflammatory peptides (AIPs) are promising therapeutics due to their specificity, efficacy, and safety. This study evaluated the cationic antimicrobial peptide IL15.3 for anti-inflammatory activity and cytocompatibility\n                    <jats:italic>in vitro<\/jats:italic>\n                    . IL15.3 demonstrated low cytotoxicity in MTT assays using RAW 264.7 macrophages, normal human dermal fibroblasts (NHDF), and HaCaT keratinocytes. In LPS-stimulated RAW 264.7 cells, IL15.3 significantly reduced nitric oxide (NO) production and reactive oxygen species (ROS) in a dose-dependent manner without affecting cell viability. qRT-PCR analysis revealed significant suppression of\n                    <jats:italic>iNOS<\/jats:italic>\n                    ,\n                    <jats:italic>COX-2<\/jats:italic>\n                    ,\n                    <jats:italic>TNF-\u03b1<\/jats:italic>\n                    , and\n                    <jats:italic>IL-6<\/jats:italic>\n                    mRNA expression, alongside downregulation of\n                    <jats:italic>NF-\u03baB<\/jats:italic>\n                    ,\n                    <jats:italic>JNK<\/jats:italic>\n                    ,\n                    <jats:italic>STAT1<\/jats:italic>\n                    , and\n                    <jats:italic>STAT3<\/jats:italic>\n                    , and a reciprocal shift in\n                    <jats:italic>Keap1<\/jats:italic>\n                    \/\n                    <jats:italic>Nrf2<\/jats:italic>\n                    expression suggestive of possible antioxidant pathway activation. Label-free proteomic profiling identified 5,191 proteins, revealing a multi-modal mechanism of action. IL15.3 treatment exclusively induced 4 anti-inflammatory proteins (ISG15, PEX14, TNIP3, PR) and upregulated negative regulators NRG1, DAB2IP, IL-18BP and SOCS5. Critically, IL15.3 suppressed key pro-inflammatory mediators including IKK\u03b2, JAK1, JAK3, JNK, and IL-1RAcP, demonstrating comprehensive modulation of NF-\u03baB, JAK\/STAT, and MAPK pathways.\n                    <jats:italic>In silico<\/jats:italic>\n                    molecular docking further predicted potential interactions of IL15.3 with iNOS and the Keap1 Kelch domain, offering preliminary structural insight consistent with its putative dual anti-inflammatory and antioxidant activity. Together, these findings indicate that IL15.3 exhibits potent anti-inflammatory and antioxidant activity through multiple mechanisms in LPS-stimulated macrophages at transcriptional and proteomic levels. The coordinated upregulation of negative regulators and suppression of central inflammatory mediators collectively suggest that IL15.3 may represent a promising therapeutic candidate for inflammatory disorders.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0361031","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:42:27Z","timestamp":1792690947000},"page":"e0361031","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["IL15.3, a synthetic antimicrobial peptide, attenuates LPS-induced inflammatory responses in RAW 264.7 macrophages via transcriptional and proteomic modulation"],"prefix":"10.1371","volume":"21","author":[{"given":"Chanapat","family":"Boonmark","sequence":"first","affiliation":[{"name":"Khon Kaen University","place":["Khon Kaen, Thailand"],"department":["Protein and Bio-Innovation Research Center for Sustainable Health (ProBISH), Faculty 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