| First Author | Paeschke A | Year | 2016 |
| Journal | Eur J Immunol | Volume | 46 |
| Issue | 3 | Pages | 619-33 |
| PubMed ID | 26578407 | Mgi Jnum | J:234519 |
| Mgi Id | MGI:5790155 | Doi | 10.1002/eji.201545892 |
| Citation | Paeschke A, et al. (2016) The immunoproteasome controls the availability of the cardioprotective pattern recognition molecule Pentraxin3. Eur J Immunol 46(3):619-33 |
| abstractText | 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. |
