title: Distinct contribution of protein kinase Cδ and protein kinase Cε in the lifespan and immune response of human blood monocyte subpopulations.
abstract: Monocytes, key components of the immune system, are a heterogeneous population comprised of classical monocytes (CD16(-) ) and non-classical monocytes (CD16(+) ). Monocytes are short lived and undergo spontaneous apoptosis, unless stimulated. Dysregulation of monocyte numbers contribute to the pathophysiology of inflammatory diseases, yet the contribution of each subset remains poorly characterized. Protein kinase C (PKC) family members are central to monocyte biology; however, their role in regulating lifespan and immune function of CD16(-) and CD16(+) monocytes has not been studied. Here, we evaluated the contribution of PKCδ and PKCε in the lifespan and immune response of both monocyte subsets. We showed that CD16(+) monocytes are more susceptible to spontaneous apoptosis because of the increased caspase-3, -8 and -9 activities accompanied by higher kinase activity of PKCδ. Silencing of PKCδ reduced apoptosis in both CD16(+) and CD16(-) monocytes. CD16(+) monocytes express significantly higher levels of PKCε and produce more tumour necrosis factor-α in CD16(+) compared with CD16(-) monocytes. Silencing of PKCε affected the survival and tumour necrosis factor-α production. These findings demonstrate a complex network with similar topography, yet unique regulatory characteristics controlling lifespan and immune response in each monocyte subset, helping define subset-specific coordination programmes controlling monocyte function.
authors.affiliation: Department of Molecular Genetics, Department of Internal Medicine, Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Yadira
authors.initials: Y
authors.lastname: Malavez
authors.forename: Oliver H
authors.initials: OH
authors.lastname: Voss
authors.forename: Martha Elba
authors.initials: ME
authors.lastname: Gonzalez-Mejia
authors.forename: Arti
authors.initials: A
authors.lastname: Parihar
authors.forename: Andrea I
authors.initials: AI
authors.lastname: Doseff
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D058851:GPI-Linked Proteins / Q000172:deficiency / Q000276:immunology; D006801:Humans; D009000:Monocytes / Q000145:classification / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D051745:Protein Kinase C-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D034622:RNA Interference; D017452:Receptors, IgG / Q000172:deficiency / Q000276:immunology; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; C497258:PRKCD protein, human; C497255:PRKCE protein, human; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: apoptosis; heterogeneous monocyte population; inflammation; protein kinase Cδ; protein kinase Cε