The Anti-Microbial Peptide (Lin-SB056-1)<sub>2</sub>-K Reduces Pro-Inflammatory Cytokine Release through Interaction with <i>Pseudomonas aeruginosa</i> Lipopolysaccharide
Lucia Grassi,
Arianna Pompilio,
Esingül Kaya,
Andrea C. Rinaldi,
Enrico Sanjust,
Giuseppantonio Maisetta,
Aurélie Crabbé,
Giovanni Di Bonaventura,
Giovanna Batoni,
Semih Esin
Affiliations
Lucia Grassi
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56123 Pisa PI, Italy
Arianna Pompilio
Department of Medical, Oral and Biotechnological Sciences, and Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti CH, Italy
Esingül Kaya
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56123 Pisa PI, Italy
Andrea C. Rinaldi
Department of Biomedical Sciences, University of Cagliari, 09142 Monserrato CA, Italy
Enrico Sanjust
Department of Biomedical Sciences, University of Cagliari, 09142 Monserrato CA, Italy
Giuseppantonio Maisetta
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56123 Pisa PI, Italy
Aurélie Crabbé
Laboratory of Pharmaceutical Microbiology, Ghent University, 9000 Gent, Belgium
Giovanni Di Bonaventura
Department of Medical, Oral and Biotechnological Sciences, and Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti CH, Italy
Giovanna Batoni
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56123 Pisa PI, Italy
Semih Esin
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56123 Pisa PI, Italy
The ability of many anti-microbial peptides (AMPs) to modulate the host immune response has highlighted their possible therapeutic use to reduce uncontrolled inflammation during chronic infections. In the present study, we examined the anti-inflammatory potential of the semi-synthetic peptide lin-SB056-1 and its dendrimeric derivative (lin-SB056-1)2-K, which were previously found to have anti-microbial activity against Pseudomonas aeruginosa in in vivo-like models mimicking the challenging environment of chronically infected lungs (i.e., artificial sputum medium and 3-D lung mucosa model). The dendrimeric derivative exerted a stronger anti-inflammatory activity than its monomeric counterpart towards lung epithelial- and macrophage-cell lines stimulated with P. aeruginosa lipopolysaccharide (LPS), based on a marked decrease (up to 80%) in the LPS-induced production of different pro-inflammatory cytokines (i.e., IL-1β, IL-6 and IL-8). Accordingly, (lin-SB056-1)2-K exhibited a stronger LPS-binding affinity than its monomeric counterpart, thereby suggesting a role of peptide/LPS neutralizing interactions in the observed anti-inflammatory effect. Along with the anti-bacterial and anti-biofilm properties, the anti-inflammatory activity of (lin-SB056-1)2-K broadens its therapeutic potential in the context of chronic (biofilm-associated) infections.
