YB-1 is an early and central mediator of bacterial and sterile inflammation in vivo

Lydia Hanssen, Christina Alidousty, Sonja Djudjaj, Björn C. Frye, Thomas Rauen, Peter Boor, Peter R. Mertens, Claudia R. Van Roeyen, Frank Tacke, Felix Heymann, Andre P. Tittel, Alexander Koch, Jürgen Floege, Tammo Ostendorf, Ute Raffetseder

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

In vitro studies identified Y-box-binding protein (YB)-1 as a key regulator of inflammatory mediators. In this study, we observed increased levels of secreted YB-1 in sera from sepsis patients. This led us to investigate the in vivo role of YB-1 in murine models of acute peritonitis following LPS injection, in sterile renal inflammation following unilateral ureteral obstruction, and in experimental pyelonephritis. LPS injection enhanced de novo secretion of YB-1 into the urine and the peritoneal fluid of LPS-treated mice. Furthermore, we could demonstrate a significant, transient upregulation and posttranslational modification (phosphorylation at serine 102) of YB-1 in renal and inflammatory cells. Increased renal cytoplasmic YB-1 amounts conferred enhanced expression of proinflammatory chemokines CCL2 and CCL5. Along these lines, heterozygous YB-1 knockout mice (YB-1+/d) that display 50% reduced YB-1 levels developed significantly lower responses to both LPS and sterile inflammation induced by unilateral ureteral obstruction. This included diminished immune cell numbers due to impaired migration propensities and reduced chemokine expression. YB-1+/d mice were protected from LPS-associated mortality (20% mortality on day 3 versus 80% in wild-type controls); however, immunosuppression in YB-1+/d animals resulted in 50% mortality. In conclusion, our findings identify YB-1 as a major, nonredundant mediator in both systemic and local inflammatory responses.

Original languageEnglish
Pages (from-to)2604-2613
Number of pages10
JournalJournal of Immunology
Volume191
Issue number5
DOIs
StatePublished - 1 Sep 2013
Externally publishedYes

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