Abstract
HDAC inhibitors have been proposed as anticancer agents. However, their roles in innate genes expression remain not well known. Cathelicidin LL-37 is one of the few human bactericidal peptides, but the regulation of histone acetylation on LL-37 expression in airway epithelium remains largely unknown. Therefore, we investigated the effects of two non-selective HDACi, trichostatin A (TSA) and sodium butyrate (SB), on the expression of the cathelicidin LL-37 in human airway epithelial cells. LL37 in human NCI-H292 airway epithelial cells and the primary cultures of normal nasal epithelial cells(PNEC) in response to HDAC inhibitors with or without poly (I:C) stimulation was assessed using real-time PCR and western blot. In parallel, IL-6 expression was evaluated by ELISA. Our results showed that HDAC inhibitors up-regulated LL-37 gene expression independent of poly (I:C) stimulation in PNEC as well as in NCI-H292 cells. HDAC inhibitors increased LL37 protein expression in NCI-H292 cells but not in PNEC. In addition, HDAC inhibitors significantly inhibited poly (I:C)-induced IL-6 production in both of the epithelial cells. In conclusion, HDAC inhibitors directly up-regulated LL-37 gene expression in human airway epithelial cells.
Highlights
Recent studies suggest that epigenetics have an important role in regulating innate immunity and that the manifestation and severity of diseases may be influenced by epigenetic factors
histone deacetylases (HDACs) inhibitors directly induce LL-37 gene expression in NCI-H292 human airway epithelial cells Antibacterial peptides are an integral part of the epithelial defence barrier that provides immediate protection against infection
To confirm the findings obtained with trichostatin A (TSA), we tested the effect of other HDAC inhibitor, sodium butyrate (SB)
Summary
Recent studies suggest that epigenetics have an important role in regulating innate immunity and that the manifestation and severity of diseases may be influenced by epigenetic factors. Epigenetic modifications play an important role in the regulation of gene expression and a common mechanism in epigenetics is the control of the accessibility of the transcriptional machinery to promoter and enhancer elements in the genome. Histone modification through reversible acetylation is a crucial event in gene transcription regulation [1,2,3]. Small changes in the HAT/HDAC balance could affect transcription of many inflammatory genes, potentially having a profound effect on the initiation and duration of inflammatory. The respiratory epithelium is an important interface with the environment and it is well accepted that the epithelium is just a physical barrier, but plays an active role in innate and adaptive immunity [7]. Cathelicidins are a family of antimicrobial peptides and LL-37, the only cathelicidin in humans, plays a critical role in the defension of epithelium against the microorganism and is produced by neutrophils, macrophages, and various epithelial cells as well [8]
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