Characterization of host defense peptide inducing compounds in human HT-29 cells: Investigating the innate human immune system as an alternative to antibiotics

Abstract

Inducing the innate human immune system's host defense peptide activity presents a novel alternative for antimicrobial therapy in the fight against antibiotic-resistant bacterial strains. The human body has only one cathelicidin host defense peptide, known as LL-37. The compound butyrate has already been identified as a positive control for inducing LL-37 gene expression, however a high-throughput screening assay has identified several additional potential compounds as possible host defense peptide inducing compounds in animal cell lines. This study investigates the efficacy of LL-37 induction for three structurally similar histone deacetylase inhibiting compounds, Mocetinostat, Chidamide, and Entinostat in an in vitro study utilizing the human HT-29 cell line. Total RNA isolation and REAL Time PCR amplification techniques were used to identify relative fold-change in gene expression. All three compounds exhibited significant fold-increase in LL-37 gene expression, with Mocetinostat demonstrating the highest efficacy out of the three compounds. The results of this investigation confirm previous findings and provide a basis for future time course and in vivo investigations on the path to utilizing the innate human immune system as a possible novel alternative to antibiotics.