scholarly journals Basal and Reovirus-Induced Beta Interferon (IFN-β) and IFN-β-Stimulated Gene Expression Are Cell Type Specific in the Cardiac Protective Response

2005 ◽  
Vol 79 (5) ◽  
pp. 2979-2987 ◽  
Author(s):  
Michael J. Stewart ◽  
Kathleen Smoak ◽  
Mary Ann Blum ◽  
Barbara Sherry
Keyword(s):  
Cardiac Myocytes ◽  
Cardiac Myocyte ◽  
Cardiac Fibroblasts ◽  
Viral Myocarditis ◽  
Cell Types ◽  
Protective Role ◽  
Cell Type ◽  
Cardiac Damage ◽  
Beta Interferon ◽  
Reovirus Replication

ABSTRACT Viral myocarditis is an important human disease, with a wide variety of viruses implicated. Cardiac myocytes are not replenished yet are critical for host survival and thus may have a unique response to infection. Previously, we determined that the extent of reovirus induction of beta interferon (IFN-β) and IFN-β-mediated protection in primary cardiac myocyte cultures was inversely correlated with the extent of reovirus-induced cardiac damage in a mouse model. Surprisingly, and in contrast, the IFN-β response did not determine reovirus replication in skeletal muscle cells. Here we compared the IFN-β response in cardiac myocytes to that in primary cardiac fibroblast cultures, a readily replenished cardiac cell type. We compared basal and reovirus-induced expression of IFN-β, IRF-7 (an interferon-stimulated gene [ISG] that further induces IFN-β), and another ISG (561) in the two cell types by using real-time reverse transcription-PCR. Basal IFN-β, IRF-7, and 561 expression was higher in cardiac myocytes than in cardiac fibroblasts. Reovirus T3D induced greater expression of IFN-β in cardiac myocytes than in cardiac fibroblasts but equivalent expression of IRF-7 and 561 in the two cell types (though fold induction for IRF-7 and 561 was higher in fibroblasts than in myocytes because of the differences in basal expression). Interestingly, while reovirus replicated to equivalent titers in cardiac myocytes and cardiac fibroblasts, removal of IFN-β resulted in 10-fold-greater reovirus replication in the fibroblasts than in the myocytes. Together the data suggest that the IFN-β response controls reovirus replication equivalently in the two cell types. In the absence of reovirus-induced IFN-β, however, reovirus replicates to higher titers in cardiac fibroblasts than in cardiac myocytes, suggesting that the higher basal IFN-β and ISG expression in myocytes may play an important protective role.

scholarly journals Basal Expression Levels of IFNAR and Jak-STAT Components Are Determinants of Cell-Type-Specific Differences in Cardiac Antiviral Responses

2007 ◽  
Vol 81 (24) ◽  
pp. 13668-13680 ◽  
Author(s):  
Jennifer Zurney ◽  
Kristina E. Howard ◽  
Barbara Sherry
Keyword(s):  
Cardiac Myocytes ◽  
Cardiac Fibroblasts ◽  
Viral Myocarditis ◽  
Cell Types ◽  
Cell Type ◽  
Organ Protection ◽  
Integrated Network ◽  
Basal Expression ◽  
Cell Type Specific ◽  
Β Receptor

ABSTRACT Viral myocarditis is an important human disease, and reovirus-induced murine myocarditis provides an excellent model system for study. Cardiac myocytes, like neurons in the central nervous system, are not replenished, yet there is no cardiac protective equivalent to the blood-brain barrier. Thus, cardiac myocytes may have evolved a unique antiviral response relative to readily replenished cell types, such as cardiac fibroblasts. Our previous comparisons of these two cell types revealed a conundrum: reovirus T3D induces more beta-interferon (IFN-β) mRNA in cardiac myocytes, yet there is a greater induction of IFN-stimulated genes (ISGs) in cardiac fibroblasts. Here, we investigated possible underlying molecular determinants. We found that greater basal expression of IFN-β in cardiac myocytes results in greater basal activated nuclear STAT1 and STAT2 and greater basal ISG mRNA expression and provides greater basal antiviral protection relative to cardiac fibroblasts. Conversely, cardiac fibroblasts express greater basal IFN-α/β receptor 1 (IFNAR1) and greater basal cytoplasmic Jak1, Tyk2, STAT2, and IRF9, leading to a greater increase in reovirus T3D- or IFN-induced nuclear activated STAT1 and STAT2 and greater induction of ISGs for a greater IFN-induced antiviral protection relative to cardiac myocytes. Our results suggest that high basal IFN-β expression in cardiac myocytes prearms this vulnerable, nonreplenishable cell type, while high basal expression of IFNAR1 and latent Jak-STAT components in adjacent cardiac fibroblasts renders these cells more responsive to IFN and prevents them from inadvertently serving as a reservoir for viral replication and spread to cardiac myocytes. These studies provide the first indication of an integrated network of cell-type-specific innate immune components for organ protection.

scholarly journals Interferon Regulatory Factor 3 Is Required for Viral Induction of Beta Interferon in Primary Cardiac Myocyte Cultures

1999 ◽  
Vol 73 (12) ◽  
pp. 10208-10213 ◽  
Author(s):  
Diana L. Noah ◽  
Mary Ann Blum ◽  
Barbara Sherry
Keyword(s):  
Cardiac Myocyte ◽  
Viral Myocarditis ◽  
Cell Types ◽  
Interferon Regulatory Factor ◽  
Dominant Negative ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
L929 Cells ◽  
Beta Interferon ◽  
And Control

ABSTRACT Viral myocarditis affects an estimated 5 to 20% of the human population. The antiviral cytokine beta interferon (IFN-β) is critical for protection against viral myocarditis in mice. That is, nonmyocarditic reoviruses induce myocarditis in mice that lack IFN-α/β, and nonmyocarditic reoviruses both induce more IFN-β and are more sensitive to the antiviral effects of IFN-β than myocarditic reoviruses in primary cardiac myocyte cultures. Induction of IFN-β in certain cell types involves viral activation of the transcription factor interferon regulatory factor 3 (IRF-3). To address whether IRF-3 can induce IFN-β in cardiac myocytes, primary cardiac myocyte cultures and control L929 cells were transfected with a plasmid constitutively expressing IRF-3. Overexpression of IRF-3 resulted in induction of IFN-β in the absence of viral infection in both cell types. To address whether IRF-3 is required for viral induction of IFN-β, cell cultures were transfected with a plasmid constitutively expressing a dominant negative IRF-3 protein. The dominant negative IRF-3 reduced reovirus induction of IFN-β in control L929 cells and completely eliminated induction in primary cardiac myocyte cultures. This provides the first identification of a cardiac cellular factor required for viral induction of IFN-β and the first report of any cell type requiring IRF-3 for this response.

scholarly journals Moderate Calcium Channel Dysfunction in Adult Mice with Inducible Cardiomyocyte-specific Excision of the cacnb2 Gene

2011 ◽  
Vol 286 (18) ◽  
pp. 15875-15882 ◽  
Author(s):  
Marcel Meissner ◽  
Petra Weissgerber ◽  
Juan E. Camacho Londoño ◽  
Jean Prenen ◽  
Sabine Link ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Cardiac Myocyte ◽  
Heart Function ◽  
Cardiac Fibroblasts ◽  
Calcium Currents ◽  
Protein Fractions ◽  
Protein Levels ◽  
Adult Mice ◽  
Embryonic Cardiomyocytes ◽  
The Difference

The major L-type voltage-gated calcium channels in heart consist of an α1C (CaV1.2) subunit usually associated with an auxiliary β subunit (CaVβ2). In embryonic cardiomyocytes, both the complete and the cardiac myocyte-specific null mutant of CaVβ2 resulted in reduction of L-type calcium currents by up to 75%, compromising heart function and causing defective remodeling of intra- and extra-embryonic blood vessels followed by embryonic death. Here we conditionally excised the CaVβ2 gene (cacnb2) specifically in cardiac myocytes of adult mice (KO). Upon gene deletion, CaVβ2 protein expression declined by >96% in isolated cardiac myocytes and by >74% in protein fractions from heart. These latter protein fractions include CaVβ2 proteins expressed in cardiac fibroblasts. Surprisingly, mice did not show any obvious impairment, although cacnb2 excision was not compensated by expression of other CaVβ proteins or changes of CaV1.2 protein levels. Calcium currents were still dihydropyridine-sensitive, but current density at 0 mV was reduced by <29%. The voltage for half-maximal activation was slightly shifted to more depolarized potentials in KO cardiomyocytes when compared with control cells, but the difference was not significant. In summary, CaVβ2 appears to be a much stronger modulator of L-type calcium currents in embryonic than in adult cardiomyocytes. Although essential for embryonic survival, CaVβ2 down-regulation in cardiomyocytes is well tolerated by the adult mice.

scholarly journals Somatostatin receptor subtype expression in the human heart: differential expression by myocytes and fibroblasts

2005 ◽  
Vol 187 (3) ◽  
pp. 379-386 ◽  
Author(s):  
William H T Smith ◽  
R Unnikrishnan Nair ◽  
Dawn Adamson ◽  
Mark T Kearney ◽  
Stephen G Ball ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Human Heart ◽  
Cardiac Fibroblasts ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Cell Types ◽  
Somatostatin Analogues ◽  
Receptor Subtypes ◽  
Somatostatin Receptor Subtypes ◽  
Human Cardiac Fibroblasts

In acromegaly, somatostatin receptor ligands (SRLs) can ameliorate left ventricular hypertrophy (LVH) and their use is associated with demonstrable improvements in various parameters of cardiac function. It remains unclear as to whether these beneficial effects are principally attributable to falling GH and IGF-I levels, or whether SRLs exert independent direct effects on the heart via somatostatin receptors. To help address this issue, we have sought to investigate somatostatin receptor expression in human heart. A human heart cDNA library was probed using PCR techniques to determine expression of somatostatin receptor subtypes. Subsequently, human heart biopsies and human cardiac fibroblasts and myocytes were analysed to determine whether expression differed between cardiac chambers or cell types. mRNAs for four of the five somatostatin receptor subtypes (sst1, sst2, sst4 and sst5) were shown to be co-expressed by the human heart. These receptors were present in both atrial and ventricular tissue. Human cardiac myocytes expressed mRNA for only sst1 and sst2, while human cardiac fibroblasts expressed all four subtypes found in whole heart tissue. The expression of functional somatostatin receptors on human cardiac fibroblasts was confirmed by mobilisation of intracellular calcium in response to somatostatin. The presence of cardiac somatostatin receptors raises the possibility of a direct effect of somatostatin analogues on the heart. Furthermore, the differential expression of somatostatin receptor subtypes by human cardiac myocytes and fibroblasts opens up the possibility of differential modulation of the cell types in the heart by subtype-specific somatostatin analogues.

scholarly journals Complex Relationship Between Cardiac Fibroblasts and Cardiomyocytes in Health and Disease

2021 ◽  
Author(s):  
Caitlin Hall ◽  
Katja Gehmlich ◽  
Chris Denning ◽  
Davor Pavlovic
Keyword(s):  
Indirect Effects ◽  
Cardiac Myocyte ◽  
Cardiac Fibroblasts ◽  
Fibroblast Proliferation ◽  
Direct And Indirect Effects ◽  
Cell Type ◽  
Myocyte Function ◽  
Health And Disease ◽  
Primary Cell Type ◽  
Use Of Models

Abstract Cardiac fibroblasts are the primary cell type responsible for deposition of extracellular matrix in the heart, providing support to the contracting myocardium and contributing to a myriad of physiological signaling processes. Despite the importance of fibrosis in processes of wound healing, excessive fibroblast proliferation and activation can lead to pathological remodeling, driving heart failure and the onset of arrhythmias. Our understanding of the mechanisms driving the cardiac fibroblast activation and proliferation is expanding, and evidence for their direct and indirect effects on cardiac myocyte function is accumulating. In this review, we focus on the importance of the fibroblast‐to‐myofibroblast transition and the cross talk of cardiac fibroblasts with cardiac myocytes. We also consider the current use of models used to explore these questions.

scholarly journals Cell type-specific roles of PAR1 in Coxsackievirus B3 infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael F. Bode ◽  
Clare M. Schmedes ◽  
Grant J. Egnatz ◽  
Vanthana Bharathi ◽  
Yohei M. Hisada ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Cardiac Fibroblasts ◽  
Coxsackievirus B3 ◽  
Poly I:C ◽  
Cell Type ◽  
Embryonic Fibroblasts ◽  
Cell Type Specific ◽  
Protease Activated Receptor 1 ◽  
Inflammatory Infiltrates ◽  
Specific Deletion

AbstractProtease-activated receptor 1 (PAR1) is widely expressed in humans and mice, and is activated by a variety of proteases, including thrombin. Recently, we showed that PAR1 contributes to the innate immune response to viral infection. Mice with a global deficiency of PAR1 expressed lower levels of CXCL10 and had increased Coxsackievirus B3 (CVB3)-induced myocarditis compared with control mice. In this study, we determined the effect of cell type-specific deletion of PAR1 in cardiac myocytes (CMs) and cardiac fibroblasts (CFs) on CVB3-induced myocarditis. Mice lacking PAR1 in either CMs or CFs exhibited increased CVB3 genomes, inflammatory infiltrates, macrophages and inflammatory mediators in the heart and increased CVB3-induced myocarditis compared with wild-type controls. Interestingly, PAR1 enhanced poly I:C induction of CXCL10 in rat CFs but not in rat neonatal CMs. Importantly, activation of PAR1 reduced CVB3 replication in murine embryonic fibroblasts and murine embryonic cardiac myocytes. In addition, we showed that PAR1 reduced autophagy in murine embryonic fibroblasts and rat H9c2 cells, which may explain how PAR1 reduces CVB3 replication. These data suggest that PAR1 on CFs protects against CVB3-induced myocarditis by enhancing the anti-viral response whereas PAR1 on both CMs and fibroblasts inhibits viral replication.

Abstract 310: Production of Basal Lamina Collagen IV by Cardiac Fibroblasts in 3-Dimensional Cultures

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Amy Bradshaw ◽  
Jessica Trombetta eSilva ◽  
Erik Eadie ◽  
Thomas K Borg
Keyword(s):  
Extracellular Matrix ◽  
Basal Lamina ◽  
Cardiac Myocyte ◽  
Structural Integrity ◽  
Cardiac Fibroblasts ◽  
Critical Role ◽  
Collagen Iv ◽  
Primary Cell ◽  
Cell Type ◽  
Primary Cell Type

Cardiac fibroblasts are generally considered the primary cell type that controls extracellular matrix homeostasis in the heart. Distinct changes in amounts and composition of extracellular matrix occur from birth to old age. Accordingly, age-dependent alterations in cardiac extracellular matrix are an important factor governing response to injury and pathological remodeling. Whereas cardiac myocytes are surrounded by a basal lamina, cardiac fibroblasts do not assemble a cell-adjacent basal lamina. Evidence is presented that in addition to fibrillar collagen production, cardiac fibroblasts are also the primary cell type responsible for the production of collagen IV. First, patterns and abundance of collagen IV in murine heart was established in sections from neonate, adult, and aged mice. Second, production of collagen IV by fibroblasts grown in 3-D fibrin gels was assessed by confocal microscopy and quantification by immmunoblot analysis. Finally, co-cultures of cardiac fibroblasts with myocytes were performed to show that fibroblasts are the primary cell type producing collagen IV under these conditions. The basal lamina of the myocytes plays a critical role in aligning and tethering myocytes together as well as making connections to the interstitial collagen fibers of the heart. Hence, production of collagen IV by cardiac fibroblasts would provide a mechanism by which cardiac fibroblasts assist in aligning and securing cardiac myocyte alignment and structural integrity via basal lamina production.

Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

1978 ◽  
Vol 36 (2) ◽  
pp. 644-645
Author(s):  
G. Rowden ◽  
M. G. Lewis ◽  
T. M. Phillips
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Cell Types ◽  
Cell Type ◽  
Electron Microscopic ◽  
La Antigen ◽  
Microscopic Studies ◽  
A Cell ◽  
C3 Receptors ◽  
Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

Protective role of peroxiredoxin-4 in heart failure

2020 ◽  
Vol 134 (1) ◽  
pp. 71-72
Author(s):  
Naseer Ahmed ◽  
Masooma Naseem ◽  
Javeria Farooq
Keyword(s):  
Heart Failure ◽  
Cardiac Fibroblasts ◽  
Protective Role ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Galectin 3 ◽  
Consequent Increase ◽  
And Oxidative Stress

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

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