Regulation of cytokine mRNA stability by IL-10

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Cytokines are important regulators of an adequate immune response. An excessive inflammatory response can lead as much as an excessive anti-inflammatory counter regulation to life threatening situations. For an appropriate therapeutical intervention it is therefore of uppermost importance to understand the regulation of pro- and anti-inflammatory cytokines. IL-10 is one of the few cytokines which can confine an inflammation. Despite of this, there is little knowledge of how IL-10 mediates this inhibitory activity on the molecular level. We could demonstrate that IL-10 decreases the mRNA stability of several important inflammatory cytokines. The stability of mRNAs can be regulated via proteins binding to AU-rich elements in cytokine mRNAs. Furthermore, the recently discovered microRNAs have been reported to regulate mRNA stability. We have identified the IL-10 regulated gene Tis11D as a candidate for mediating the effects of IL-10 on AU-rich elements. Furthermore, we could show that IL-10 can prevent the down regulation of mi-R16. We therefore want to analyse the functional role of these factors in mRNA stability regulation of cytokine mRNAs.