Lysozyme-Induced Transcriptional Regulation of TNF-α Pathway Genes in Cells of the Monocyte Lineage

Int J Mol Sci. 2019 Nov 5;20(21):5502. doi: 10.3390/ijms20215502.

Abstract

Lysozyme is one of the most important anti-bacterial effectors in the innate immune system of animals. Besides its direct antibacterial enzymatic activity, lysozyme displays other biological properties, pointing toward a significant anti-inflammatory effect, many aspects of which are still elusive. Here we investigate the perturbation of gene expression profiles induced by lysozyme in a monocyte cell line in vitro considering a perspective as broad as the whole transcriptome profiling. The results of the RNA-seq experiment show that lysozyme induces transcriptional modulation of the TNF-α/IL-1β pathway genes in U937 monocytes. The analysis of transcriptomic profiles with IPA® identified a simple but robust molecular network of genes, in which the regulation trends are fully consistent with the anti-inflammatory activity of lysozyme. This study provides the first evidence in support of the anti-inflammatory action of lysozyme on the basis of transcriptomic regulation data resulting from the broad perspective of a whole-transcriptome profiling. Such important effects can be achieved with the supplementation of relatively low concentrations of lysozyme, for a short time of exposure. These new insights allow the potential of lysozyme in pharmacological applications to be better exploited.

Keywords: IL-1β; RNA-sequencing; TNF-α; inflammation; lysozyme; proteome profiling; whole transcriptome profiling.

MeSH terms

  • Cell Line
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Muramidase / immunology*
  • Signal Transduction
  • Transcriptional Activation*
  • Transcriptome*
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Muramidase