| First Author | Wang J | Year | 2017 |
| Journal | J Cell Mol Med | Volume | 21 |
| Issue | 12 | Pages | 3494-3505 |
| PubMed ID | 28664613 | Mgi Jnum | J:319585 |
| Mgi Id | MGI:6726728 | Doi | 10.1111/jcmm.13260 |
| Citation | Wang J, et al. (2017) YB-1 orchestrates onset and resolution of renal inflammation via IL10 gene regulation. J Cell Mol Med 21(12):3494-3505 |
| abstractText | 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. |
