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Peer-reviewedCC BYPLOS One

IL15.3, a synthetic antimicrobial peptide, attenuates LPS-induced inflammatory responses in RAW 264.7 macrophages via transcriptional and proteomic modulation

  • Chanapat Boonmark1
  • Sittiruk Roytrakul2
  • Fasawanya Saengyotha1
  • Anupong Tankrathok1,3
  • Anuwat Wanthong1,4
  • Jureerut Daduang5
  • Sakda Daduang1,6
  • Arunrat Chaveerach7
  • Nisachon Jangpromma1,8
8 affiliations
  1. 1Protein and Bio-Innovation Research Center for Sustainable Health (ProBISH), Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.
  2. 2National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.
  3. 3Faculty of Agricultural Technology, Department of Biotechnology, Kalasin University, Kalasin, Thailand.
  4. 4Department of Biology, Faculty of Science, Mahasarakham University, Mahasarakham, Thailand.
  5. 5Department of Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
  6. 6Department of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand.
  7. 7Department of Biology, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.
  8. 8Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.
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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.

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Cite

BibTeXRIS
BibTeX
@article{boonmark2026il153,
  title = {{IL15.3, a synthetic antimicrobial peptide, attenuates LPS-induced inflammatory responses in RAW 264.7 macrophages via transcriptional and proteomic modulation}},
  author = {Chanapat Boonmark and Sittiruk Roytrakul and Fasawanya Saengyotha and Anupong Tankrathok and Anuwat Wanthong and Jureerut Daduang and Sakda Daduang and Arunrat Chaveerach and Nisachon Jangpromma},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0361031},
  url = {https://doi.org/10.1371/journal.pone.0361031},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - IL15.3, a synthetic antimicrobial peptide, attenuates LPS-induced inflammatory responses in RAW 264.7 macrophages via transcriptional and proteomic modulation
AU  - Chanapat Boonmark
AU  - Sittiruk Roytrakul
AU  - Fasawanya Saengyotha
AU  - Anupong Tankrathok
AU  - Anuwat Wanthong
AU  - Jureerut Daduang
AU  - Sakda Daduang
AU  - Arunrat Chaveerach
AU  - Nisachon Jangpromma
PY  - 2026
DA  - 2026/10/22
JO  - PLOS One
DO  - 10.1371/journal.pone.0361031
UR  - https://doi.org/10.1371/journal.pone.0361031
AB  - 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.
SN  - 1932-6203
ER  -