Mrp-8 and-14 mediate CNS injury in focal cerebral ischemia

作者：Ziegler Gina; Prinz Vincent; Albrecht Marcus W; Harhausen Denise; Khojasteh Uldus; Nacken Wolfgang; Endres Matthias; Dirnagl Ulrich; Nietfeld Wilfried; Trendelenburg George^*

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2009, 1792(12): 1198-1204.

DOI：10.1016/j.bbadis.2009.10.003

• S100A8
• S100A9
• Toll-like receptor
• MCAO
• Knockout mice

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.

• 出版日期2009-12