title: NF-κB activation is cell type-specific in the heart.
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.
authors.affiliation: Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
authors.forename: Efraín E
authors.initials: EE
authors.lastname: Rivera-Serrano
authors.affiliation: Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. Electronic address: barbara_sherry@ncsu.edu.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sherry
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D006056:Golgi Apparatus / Q000378:metabolism / Q000821:virology; D006321:Heart / Q000821:virology*; D006801:Humans; D012089:Mammalian orthoreovirus 3 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000821:virology; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D012088:Reoviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B
keywords: Cardiac fibroblast; Cardiac myocyte; Cardiomyocyte; Golgi; Heart; Myocarditis; NF-κB; Reovirus