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Immunol."],"abstract":"<jats:p>A 110-amino acid precursor of dermcidin (pre-dermcidin, pre-DCD) with a 19-residue N-terminal leader signal sequence can be secreted by human eccrine sweat glands as a leader-less pro-domain-containing peptide (pro-DCD), which is enzymatically cleaved to generate C-terminal anti-microbial peptides (dermcidin-1, DCD-1) capable of killing various bacteria. Previously, it was unknown whether pro-DCD could be pharmacologically developed as potential therapeutics for lethal sepsis. Here, we demonstrated that pharmacological suppression of pro-DCD with polyclonal antibodies worsened sepsis-induced inflammation and liver injury, whereas supplementation of pro-DCD or its PEGylation derivatives significantly protected against sepsis, even when given 2\u201324 h after disease onset. These protective effects were associated with a significant reduction in circulating levels of surrogate biomarkers [e.g., Granulocyte Colony Stimulating Factor (G-CSF), Interleukin-6 (IL-6), keratinocytes-derived chemokine (KC), Monocyte Chemoattractant Protein 1 (MCP-1), Macrophage Inflammatory Protein-2 (MIP-2), and Soluble Tumor Necrosis Factor Receptor I (sTNFRI)], tissue injury, and blood bacterial counts. Although pro-DCD or its PEGylation derivatives failed to directly kill bacteria across a wide range of concentrations, they were able to activate microtubule-associated protein 1A\/1B-light chain 3 (LC3), a marker of autophagy and phagosome maturation in LC3-associated bacterial phagocytosis. Our findings suggest that pro-DCD-derived agents hold promise as potential therapies for clinical sepsis.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1621633","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:36:35Z","timestamp":1749015395000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pro-dermcidin and derivatives as potential therapeutics for lethal experimental sepsis"],"prefix":"10.3389","volume":"16","author":[{"given":"Weiqiang","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoling","family":"Qiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassie 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