The research group studied the TMA analogues generated by the previous project FFC#1/2016. In response to cellular stress, the NF-kB protein complex binds to DNA by activating the transcription of genes involved in the inflammatory response, such as interleukin-8 (IL-8). A molecule capable of inhibiting NF-kB/DNA complex would act as an anti-inflammatory agent. To evaluate the inhibitory capacity of the analogues synthesized by the research team, the mobility shift electrophoresis assay (EMSA) was applied to study the interaction between protein and DNA. The TMA analogs that showed inhibitory activity were then tested in-vitro (on cell lines derived from CF patient cells) and in-vivo (on a mouse model of acute and chronic lung inflammation). Gene expression analysis on IL-8 gene allowed the identification of three analogues which were further tested in-vivo. The in-vitro experiments allowed the identification of two non-toxic compounds on which the research group is completing in-vivo pharmacokinetic studies and further toxicity tests.

Pubblications

• Cabrini G, Rimessi A, Borgatti M et al. Role of Cystic Fibrosis Bronchial Epithelium in Neutrophil Chemotaxis, Mucosal Immunology, 2020 Aug 4;11:1438