title: The calcineurin inhibitor RCAN1 is involved in cultured macrophage and in vivo immune response.
abstract: Studies on the role of regulator of calcineurin 1 (RCAN1) in immunity are limited, but have demonstrated an involvement in T-lymphocyte function. Here, we expand these studies to macrophages and in vivo infection. The treatment of RAW and primary mouse macrophages with lipopolysaccharide from Escherichia coli strongly induced RCAN1 isoform 4 (RCAN1-4), but not isoform 1. RCAN1-4 induction involved calcium, calcineurin, and reactive oxygen species. Subsequent analysis with whole bacteria including gram-negative E. coli and gram-positive Staphylococcus aureus revealed strong RCAN1-4 inductions by both, and where tested, dependence on calcium. Staphylococcus aureus cell wall components peptidoglycan and lipoteichoic acid also strongly induced RCAN1-4. In vivo, a significant induction in the proinflammatory cytokines monocyte chemotactic protein-1, interleukin-6, interferon-γ, and tumor necrosis factor-α was observed in knockout (KO) lung vs. wild-type (WT) mice 7 days after nasal infection with Fransicella tularensis. This induction was not accompanied by a significant increase in F. tularensis burden in the KO lung. Additionally, a modest increase in respiratory burst activity in KO vs. WT macrophages was observed. Combined, these studies indicate that RCAN1 is involved in macrophage and the overall in vivo immune response, and provide additional evidence that RCAN1 plays an important role in cell immunity and infectious disease.
authors.affiliation: Center for Immunology and Microbial Disease, The Albany Medical College, Albany, NY, USA.
authors.forename: Dipti L
authors.initials: DL
authors.lastname: Bhoiwala
authors.forename: Vishnu
authors.initials: V
authors.lastname: Kannabiran
authors.forename: Shazneen F
authors.initials: SF
authors.lastname: Hushmendy
authors.forename: Amy
authors.initials: A
authors.lastname: Hahn
authors.forename: Devang L
authors.initials: DL
authors.lastname: Bhoiwala
authors.forename: Janet M
authors.initials: JM
authors.lastname: Heuring
authors.forename: Dana R
authors.initials: DR
authors.lastname: Crawford
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005604:Francisella tularensis / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D014406:Tularemia / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D065095:Calcineurin Inhibitors; D002135:Calcium-Binding Proteins; D016207:Cytokines; C511512:DSCR1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D009124:Muscle Proteins; D010457:Peptidoglycan; D014409:Tumor Necrosis Factor-alpha