{ "abstract": "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 in vitro. 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 iNOS, COX-2, TNF-α, and IL-6 mRNA expression, alongside downregulation of NF-κB, JNK, STAT1, and STAT3, and a reciprocal shift in Keap1/Nrf2 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 IKKβ, JAK1, JAK3, JNK, and IL-1RAcP, demonstrating comprehensive modulation of NF-κB, JAK/STAT, and MAPK pathways. In silico 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.", "abstract_shown": true, "affiliations": [ "Protein and Bio-Innovation Research Center for Sustainable Health (ProBISH), Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.", "National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.", "Faculty of Agricultural Technology, Department of Biotechnology, Kalasin University, Kalasin, Thailand.", "Department of Biology, Faculty of Science, Mahasarakham University, Mahasarakham, Thailand.", "Department of Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.", "Department of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand.", "Department of Biology, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.", "Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand." ], "article_type": "Research Article", "arxiv": null, "author_total": 9, "authors": [ { "affs": [ 0 ], "name": "Chanapat Boonmark" }, { "affs": [ 1 ], "name": "Sittiruk Roytrakul" }, { "affs": [ 0 ], "name": "Fasawanya Saengyotha" }, { "affs": [ 0, 2 ], "name": "Anupong Tankrathok", "orcid": "0000-0002-4636-6142" }, { "affs": [ 0, 3 ], "name": "Anuwat Wanthong" }, { "affs": [ 4 ], "name": "Jureerut Daduang" }, { "affs": [ 0, 5 ], "name": "Sakda Daduang" }, { "affs": [ 6 ], "name": "Arunrat Chaveerach" }, { "affs": [ 0, 7 ], "name": "Nisachon Jangpromma", "orcid": "0000-0002-2071-2406" } ], "bibtex": "https://research.draconitic.com/paper/aq6ypyrsd7rtz.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0361031", "fulltext_url": "https://europepmc.org/articles/PMC13690211", "id": "aq6ypyrsd7rtz", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0361031", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2404|Antimicrobial Peptides and Activities" ], [ "plos", "/Biology and life sciences/Biochemistry/Neurochemistry/Neurochemicals/Nitric oxide" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/DNA-binding proteins/Transcription factors" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Regulatory proteins/Transcription factors" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling/Redox signaling" ], [ "plos", "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling/Signaling cascades/Protein kinase signaling cascade" ], [ "plos", "/Biology and life sciences/Developmental biology/Molecular development/Cytokines" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Transcription factors" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Immunology/Immune response/Inflammation" ], [ "plos", "/Biology and life sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Biology and life sciences/Neuroscience/Neurochemistry/Neurochemicals/Nitric oxide" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Cytokines" ], [ "plos", "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Inflammation" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Medicine and health sciences/Immunology/Immune response/Inflammation" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Medicine and health sciences/Medical conditions/Inflammatory diseases" ] ], "openalex": "W7223236474", "pdf_url": "https://europepmc.org/articles/PMC13690211?pdf=render", "pmcid": "PMC13690211", "pmid": "42911985", "published": "2026-10-22", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/aq6ypyrsd7rtz.ris", "sources": [ { "first_seen": "2026-10-30T12:17:23Z", "native_id": "10.1371/journal.pone.0361031", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0361031" }, { "first_seen": "2026-10-30T12:20:10Z", "native_id": "MED:42911985", "source": "europepmc", "url": "https://europepmc.org/article/MED/42911985" } ], "subjects": [ { "field": "biology", "origin": "plos:cell biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" } ], "title": "IL15.3, a synthetic antimicrobial peptide, attenuates LPS-induced inflammatory responses in RAW 264.7 macrophages via transcriptional and proteomic modulation", "title_text": "IL15.3, a synthetic antimicrobial peptide, attenuates LPS-induced inflammatory responses in RAW 264.7 macrophages via transcriptional and proteomic modulation", "type": "peer-reviewed", "updated_at": "2026-10-30T12:20:10Z", "url": "https://research.draconitic.com/paper/aq6ypyrsd7rtz", "venue": "PLOS One", "versions": [] }