The potential role of antimicrobial peptides from wasp as regulators of the fibrotic process in idiopathic pulmonary fibrosis

Antimicrobial peptides are small molecules that engage in the innate immune response of all vertebrate and invertebrate species, endowed with antimicrobial, antiparasitic, antiviral and anti-inflammatory activity. This project aims to analyze some of those properties of four wasp-derived peptides in in vitro assays and evaluate its mechanisms in bleomycin treated BALB\c mice idiopathic pulmonary fibrosis model. In in vitro assays, we evaluated the peptides cellular toxicity and immunomodulatory activity in LPS-stimulated murine peritoneal macrophages. Then, we selected two peptides that showed better anti-inflammatory activity, demonstrated by the reduction of TNF-α release, DL14 and Protonectin. For the in vivo experiment, we instilled bleomycin intratracheally and five days later, at the beginning of the fibrotic process, mice were weighted and treated with the peptides at 25µM every three days. At the 30th day after bleomycin treatment, ventilatory mechanics, pro-inflammatory and pro-fibrotic cytokines were evaluated for these animals. Weight, survival rate and pulmonary density were followed for the entire experimental time. Although peptides did not promote any significant changes in the cytokines production profile, they have shown to improve the respiratory capacity with enhanced results promoted by DL14. This peptide has also demonstrated less toxicity, demonstrated by the weight stability and lower mortality rate. Therefore, DL14 may be a potential regulator of the immune response that is involved in the maintenance of fibrotic process, thus a potential target for further pharmacological studies.