title: Immunomodulatory and Anti-inflammatory Activity in Vitro and in Vivo of a Novel Antimicrobial Candidate.
abstract: The synthetic antimicrobial peptide SET-M33 has strong activity against bacterial infections caused by Gram-negative bacteria. It is currently in preclinical development as a new drug to treat lung infections caused by Gram-negative bacteria. Here we report its strong anti-inflammatory activity in terms of reduced expression of a number of cytokines, enzymes, and signal transduction factors involved in inflammation triggered by LPS from Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli Sixteen cytokines and other major agents involved in inflammation were analyzed in macrophages and bronchial cells after stimulation with LPS and incubation with SET-M33. The bronchial cells were obtained from a cystic fibrosis patient. A number of these proteins showed up to 100% reduction in expression as measured by RT-PCR, Western blotting, or Luminex technology. LPS neutralization was also demonstrated in vivo by challenging bronchoalveolar lavage of SET-M33-treated mice with LPS, which led to a sharp reduction in TNF-α with respect to non-SET-M33-treated animals. We also describe a strong activity of SET-M33 in stimulating cell migration of keratinocytes in wound healing experiments in vitro, demonstrating a powerful immunomodulatory action generally characteristic of molecules taking part in innate immunity.
authors.affiliation: From the Department of Medical Biotechnology, University of Siena, via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Jlenia
authors.initials: J
authors.lastname: Brunetti
authors.affiliation: From the Department of Medical Biotechnology, University of Siena, via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Roscia
authors.affiliation: the Department of Life Sciences and Biotechnology, University of Ferrara, via Fossato di Mortara 74, 44121 Ferrara, Italy, and.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.affiliation: the Department of Life Sciences and Biotechnology, University of Ferrara, via Fossato di Mortara 74, 44121 Ferrara, Italy, and.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.affiliation: From the Department of Medical Biotechnology, University of Siena, via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Leila
authors.initials: L
authors.lastname: Quercini
authors.affiliation: SetLance srl, via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Falciani
authors.affiliation: From the Department of Medical Biotechnology, University of Siena, via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Bracci
authors.affiliation: From the Department of Medical Biotechnology, University of Siena, via Aldo Moro 2, 53100 Siena, Italy, pinia@unisi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pini
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001980:Bronchi / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007155:Immunologic Factors; D008070:Lipopolysaccharides
keywords: LPS; anti-inflammatory agents; antimicrobial peptide (AMP); drug discovery; infectious disease; inflammation