NF-κB activation is cell type-specific in the heart

Virology. 2017 Feb;502:133-143. doi: 10.1016/j.virol.2016.12.022. Epub 2016 Dec 30.

Abstract

Viral myocarditis is common and can progress to cardiac failure. Cardiac cell pro-inflammatory responses are critical for viral clearance, however sustained inflammatory responses contribute to cardiac damage. The transcription factor NF-κB regulates expression of many pro-inflammatory cytokines, but basal and induced activation of NF-κB in different cardiac cell types have not been compared. Here, we used primary cultures of cardiac myocytes and cardiac fibroblasts to identify cardiac cell type-specific events. We show that while viral infection readily stimulates activation of NF-κB in cardiac fibroblasts, cardiac myocytes are largely recalcitrant to activation of NF-κB. Moreover, we show that cardiac myocyte subpopulations differ in their NF-κB subcellular localization and identify the cis-Golgi as a cardiac myocyte-specific host compartment. Together, results indicate that NF-κB-dependent signaling in the heart is cardiac cell type-specific, likely reflecting mechanisms that have evolved to balance responses that can be either protective or damaging to the heart.

Keywords: Cardiac fibroblast; Cardiac myocyte; Cardiomyocyte; Golgi; Heart; Myocarditis; NF-κB; Reovirus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Fibroblasts / metabolism
  • Fibroblasts / virology
  • Golgi Apparatus / metabolism
  • Golgi Apparatus / virology
  • Heart / virology*
  • Humans
  • Mammalian orthoreovirus 3 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / virology
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Organ Specificity
  • Reoviridae Infections / genetics
  • Reoviridae Infections / metabolism*
  • Reoviridae Infections / virology
  • Signal Transduction

Substances

  • NF-kappa B