RGD Reference Report - YB-1 orchestrates onset and resolution of renal inflammation via IL10 gene regulation. - Rat Genome Database

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YB-1 orchestrates onset and resolution of renal inflammation via IL10 gene regulation.

Authors: Wang, Jialin  Djudjaj, Sonja  Gibbert, Lydia  Lennartz, Vera  Breitkopf, Daniel M  Rauen, Thomas  Hermert, Daniela  Martin, Ina V  Boor, Peter  Braun, Gerald S  Floege, Jürgen  Ostendorf, Tammo  Raffetseder, Ute 
Citation: Wang J, etal., J Cell Mol Med. 2017 Dec;21(12):3494-3505. doi: 10.1111/jcmm.13260. Epub 2017 Jun 30.
RGD ID: 14975137
Pubmed: PMID:28664613   (View Abstract at PubMed)
PMCID: PMC5706504   (View Article at PubMed Central)
DOI: DOI:10.1111/jcmm.13260   (Journal Full-text)

The Y-box-binding protein (YB)-1 plays a non-redundant role in both systemic and local inflammatory response. We analysed YB-1-mediated expression of the immune regulatory cytokine IL-10 in both LPS and sterile inflammation induced by unilateral renal ischaemia-reperfusion (I/R) and found an important role of YB-1 not only in the onset but also in the resolution of inflammation in kidneys. Within a decisive cis-regulatory region of the IL10 gene locus, the fourth intron, we identified and characterized an operative YB-1 binding site via gel shift experiments and reporter assays in immune and different renal cells. In vivo, YB-1 phosphorylated at serine 102 localized to the fourth intron, which was paralleled by enhanced IL-10 mRNA expression in mice following LPS challenge and in I/R. Mice with half-maximal expression of YB-1 (Yb1+/- ) had diminished IL-10 expression upon LPS challenge. In I/R, Yb1+/- mice exhibited ameliorated kidney injury/inflammation in the early-phase (days 1 and 5), however showed aggravated long-term damage (day 21) with increased expression of IL-10 and other known mediators of renal injury and inflammation. In conclusion, these data support the notion that there are context-specific decisions concerning YB-1 function and that a fine-tuning of YB-1, for example, via a post-translational modification regulates its activity and/or localization that is crucial for systemic processes such as inflammation.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Il10  (interleukin 10)

Genes (Mus musculus)
Il10  (interleukin 10)

Genes (Homo sapiens)
IL10  (interleukin 10)


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