title: The immunoproteasome controls the availability of the cardioprotective pattern recognition molecule Pentraxin3.
abstract: Cardiomyocyte death as a result of viral infection is an excellent model for dissecting the inflammatory stress response that occurs in heart tissue. We reported earlier that a specific proteasome isoform, the immunoproteasome, prevents exacerbation of coxsackievirus B3 (CVB3)-induced myocardial destruction and preserves cell vitality in heart tissue inflammation. Following the aim to decipher molecular targets of immunoproteasome-dependent proteolysis, we investigated the function and regulation of the soluble PRR Pentraxin3 (PTX3). We show that the ablation of PTX3 in mice aggravated CVB3-triggered inflammatory injury of heart tissue, without having any significant effect on viral titers. Thus, there might be a role of PTX3 in preventing damage-associated molecular pattern-induced cell death. We found that the catalytic activity of the immunoproteasome subunit LMP7 regulates the timely availability of factors controlling PTX3 production. We report on immunoproteasome-dependent alteration of ERK1/2 and p38MAPKs, which were both found to be involved in PTX3 expression control. Our finding of a cardioprotective function of immunoproteasome-dependent PTX3 expression revealed a crucial mechanism of the stress-induced damage response in myocardial inflammation. In addition to antigen presentation and cytokine production, proteolysis by the immunoproteasome can also regulate the innate immune response during viral infection.
authors.affiliation: Institut für Biochemie, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Paeschke
authors.affiliation: Institut für Biochemie, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Possehl
authors.affiliation: Institut für Molekulare Pathologie, Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.affiliation: Institut für Biochemie, Charité Universitätsmedizin Berlin, Berlin, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Side Berlin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Voss
authors.affiliation: Institut für Biochemie, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Karolin
authors.initials: K
authors.lastname: Voss
authors.affiliation: Institut für Biochemie, Charité Universitätsmedizin Berlin, Berlin, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Side Berlin, Berlin, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Kespohl
authors.affiliation: Institut für Molekulare Pathologie, Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Sauter
authors.affiliation: Leiden Institute of Chemistry, Leiden, the Netherlands.
authors.forename: Hermen S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: Institut für Biochemie, Charité Universitätsmedizin Berlin, Berlin, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Side Berlin, Berlin, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Althof
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.affiliation: Institut für Biochemie, Charité Universitätsmedizin Berlin, Berlin, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Side Berlin, Berlin, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Voigt
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000276:immunology / Q000821:virology; D004195:Disease Models, Animal; D006321:Heart / Q000033:anatomy & histology / Q000821:virology; D007113:Immunity, Innate; D007249:Inflammation / Q000821:virology; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D009205:Myocarditis / Q000276:immunology / Q000821:virology; D009206:Myocardium / Q000276:immunology; D032383:Myocytes, Cardiac / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D059748:Proteolysis; D013312:Stress, Physiological; D019562:Viral Load; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D046988:Proteasome Endopeptidase Complex; D000099153:Pentraxins; C077436:LMP7 protein
keywords: Infection; Inflammation; Innate immunity; Myocarditis; Pentraxin3; Proteasome; Stress response; Virus