%0 Journal Article %T G¦Á12 Regulates Interleukin-8 Expression after Epithelial Cell Injury %A Alexandra K. Kim %A Barrett Richard %A Ilene Boucher %A Wanfeng Yu %A Tianqing Kong %A Bradley M. Denker %J Open Journal of Pathology %P 154-161 %@ 2164-6783 %D 2016 %I Scientific Research Publishing %R 10.4236/ojpathology.2016.63018 %X Acute kidney injury (AKI) is common in hospitalized patients and is strongly correlated with increased morbidity, mortality, and prolonged hospitalization. However, signals that determine whether injured tissues following AKI will repair or fibrose and lead to chronic kidney disease (CKD) are not well defined. Numerous cytokines are activated at various times after injury and recruit inflammatory cells. Interleukin-8 (IL-8) is upregulated following activation of G¦Á12 by H2O2, a reactive oxygen species (ROS). Herein, we study this occurrence in vitro and in vivo. IL-8 was measured by ELISA in G¦Á12-silenced (si-G¦Á12) and inducible QL¦Á12 (constitutively active G¦Á12) Madin-Darby Canine Kidney (QL¦Á12-MDCK) cell lines after H2O2/catalase cell injury. QL¦Á12- and si-G¦Á12 MDCK cells showed time-, agonist- and G¦Á12-dependent increases in IL-8 mRNA and protein. G¦Á12-silenced MDCK cells demonstrated lower IL-8 expression and blunted IL-8 increases. In transgenic mice (QL¦Á12¦ÃGTCre+, proximal tubule Q¦Á12 expression) ischemia reperfusion injury led to significant upregulation of CXCL-1 (IL-8 homologue) at 48 hours that was not observed in G¦Á12 knockout mice. Macrophages in renal cells from these mice were imaged by immunofluorescent microscopy and QL¦Á12¦ÃGTCre+ showed increased macrophage infiltration. We demonstrate that IL-8 is a critical link between H2O2 stimulated G¦Á12 and renal injury. G¦Á12 activation led to increased IL-8 expression, a potent mediator of inflammation after injury. Future studies targeting G¦Á12 for inhibition after injury may blunt the IL-8 response and allow for organ recovery. %K G¦Á12 %K Interleukin-8 %K Acute Kidney Injury %K Inflammation %K Fibrosis %U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=68158