title: Protein kinase cα regulates the expression of complement receptor Ig in human monocyte-derived macrophages.
abstract: The complement receptor Ig (CRIg) is selectively expressed by macrophages. This receptor not only promotes the rapid phagocytosis of bacteria by macrophages but also has anti-inflammatory and immunosuppressive functions. Previous findings have suggested that protein kinase C (PKC) may be involved in the regulation of CRIg expression in human macrophages. We have now examined the role of PKCα in CRIg expression in human monocyte-derived macrophages (MDM). Macrophages nucleofected with plasmid containing short hairpin RNA against PKCα showed markedly reduced expression of PKCα, but normal PKCζ expression, by Western blotting analysis, and vice versa. PKCα-deficient MDM showed increased expression of CRIg mRNA and protein (both the long and short form), an increase in phagocytosis of complement-opsonized Candida albicans, and decreased production of TNF-α and IL-6. TNF-α caused a marked decrease in CRIg expression, and addition of anti-TNF mAb to the TNF-α-producing MDMs increased CRIg expression. PKCα-deficient macrophages also showed significantly less bacterial LPS-induced downregulation of CRIg. In contrast, cells deficient in PKCα showed decreased expression of CR type 3 (CR3) and decreased production of TNF-α and IL-6 in response to LPS. MDM developed under conditions that increased expression of CRIg over CR3 showed significantly reduced production of TNF-α in response to opsonized C. albicans. The findings indicate that PKCα promotes the downregulation of CRIg and upregulation of CR3 expression and TNF-α and IL-6 production, a mechanism that may promote inflammation.
authors: Department of Immunopathology, SA Pathology, Women's and Children's Hospital, North Adelaide, Adelaide, South Australia 5006, Australia; School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, South Australia 5005, Australia;
authors: Yuefang
authors: Y
authors: Ma
authors: Department of Immunopathology, SA Pathology, Women's and Children's Hospital, North Adelaide, Adelaide, South Australia 5006, Australia; School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, South Australia 5005, Australia; Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand;
authors: Kanchana
authors: K
authors: Usuwanthim
authors: Department of Immunopathology, SA Pathology, Women's and Children's Hospital, North Adelaide, Adelaide, South Australia 5006, Australia; School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, South Australia 5005, Australia; School of Biological Science, Flinders University, Bedford Park, South Australia 5042, Australia;
authors: Usma
authors: U
authors: Munawara
authors: Department of Immunopathology, SA Pathology, Women's and Children's Hospital, North Adelaide, Adelaide, South Australia 5006, Australia; School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, South Australia 5005, Australia;
authors: Alex
authors: A
authors: Quach
authors: Department of Immunopathology, SA Pathology, Women's and Children's Hospital, North Adelaide, Adelaide, South Australia 5006, Australia; School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, South Australia 5005, Australia; Children's Medical Research Institute, University of Sydney, Westmead, New South Wales 2145, Australia;
authors: Nick N
authors: NN
authors: Gorgani
authors: School of Biological Science, Flinders University, Bedford Park, South Australia 5042, Australia;
authors: Catherine A
authors: CA
authors: Abbott
authors: Department of Immunopathology, SA Pathology, Women's and Children's Hospital, North Adelaide, Adelaide, South Australia 5006, Australia; School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, South Australia 5005, Australia;
authors: Charles S
authors: CS
authors: Hii
authors: Department of Immunopathology, SA Pathology, Women's and Children's Hospital, North Adelaide, Adelaide, South Australia 5006, Australia; School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, South Australia 5005, Australia; School of Molecular Biosciences, University of Adelaide, Adelaide, South Australia 5005, Australia; and School of Pharmaceutical and Medical Science, University of South Australia, Adelaide, South Australia 5001, Australia antonio.ferrante@adelaide.edu.au.
authors: Antonio
authors: A
authors: Ferrante
mesh_terms: D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D015153:Blotting, Western; D002176:Candida albicans / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000276:immunology / Q000494:pharmacology; D015536:Down-Regulation / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D034622:RNA Interference; D011951:Receptors, Complement / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D014409:Tumor Necrosis Factor-alpha; C414427:VSIG4 protein, human; D003907:Dexamethasone; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha