Immunomodulatory and anti-inflammatory activity in vitro and in vivo of a novel antimicrobial candidate
The synthetic antimicrobial peptide SET-M33 has strong activity against bacterial infections due to 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 lipopolysaccharides (LPS) from P. aeruginosa, K. pneumoniae and E. 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 blot 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 strong activity of SET-M33 in stimulating cell migration of keratinocytes in wound healing experiments in vitro, demonstrating powerful immunomodulatory action generally characteristic of molecules taking part in innate immunity.
Jlenia Brunetti, Giulia Roscia, Ilaria Lampronti, Roberto Gambari, Leila Quercini, Chiara Falciani, Luisa Bracci and Alessandro Pini
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