| First Author | Ziegler G | Year | 2009 |
| Journal | Biochim Biophys Acta | Volume | 1792 |
| Issue | 12 | Pages | 1198-204 |
| PubMed ID | 19835955 | Mgi Jnum | J:164831 |
| Mgi Id | MGI:4835374 | Doi | 10.1016/j.bbadis.2009.10.003 |
| Citation | Ziegler G, et al. (2009) Mrp-8 and -14 mediate CNS injury in focal cerebral ischemia. Biochim Biophys Acta 1792(12):1198-204 |
| abstractText | Several reports have recently demonstrated a detrimental role of Toll-like receptors (TLR) in cerebral ischemia, while there is little information about the endogenous ligands which activate TLR-signaling. The myeloid related proteins-8 and-14 (Mrp8/S100A8; Mrp14/S100A9) have recently been characterized as endogenous TLR4-agonists, and thus may mediate TLR-activation in cerebral ischemia. Interestingly, not only TLR-mRNAs, but also Mrp8 and Mrp14 mRNA were found to be induced in mouse brain between 3 and 48 h after transient 1 h focal cerebral ischemia/reperfusion. Mrp-protein was expressed in the ischemic hemisphere, and co-labeled with CD11b-positive cells. To test the hypothesis that Mrp-signaling contributes to the postischemic brain damage, we subjected Mrp14-deficient mice, which also lack Mrp8 protein expression, to focal cerebral ischemia. Mrp14-deficient mice had significantly smaller lesion volumes when compared to wild-type littermates (130+/-16 mm(3) vs. 105+/-28 mm(3)) at 2 days after transient focal cerebral ischemia (1 h), less brain swelling, and a reduced macrophage/microglia cell count in the ischemic hemisphere. We conclude that upregulation and signaling of Mrp-8 and-14 contribute to neuroinflammation and the progression of ischemic damage. |
