CD14-dependent alterations in c-Jun expression and phosphorylation in the liver after injury

Abstract

CD14-mediated activation of proinflammatory genes may contribute to the pathogenesis of some distant organs after burn injury. The regulation of CD14 and its role in the immediate-early response of c-Jun in the liver after burn injury were investigated in this study. The identification of the differentially displayed CD14 mRNA in the lungs after 18% total body surface area burn was confirmed by a RT-PCR analysis demonstrating a rapid and transient induction of CD14 mRNA in the liver and lungs of mice after injury. Immunohistochemical analysis revealed a peak induction of CD14 reactivity in cells appearing to be Kupffer cells at day 1 after injury. In addition, an augmented and delayed induction of c-Jun mRNA was observed in the liver of CD14 knock-out (KO) mice compared to wild type (WT) controls. Furthermore, Western blot analysis revealed that the induction of phosphorylated (serine 63 or serine 73) c-Jun was decreased in CD14 KO mice 1 day after injury compared to WT controls (Figure below). This study provides evidence that injury elicits CD14 induction as well as hyperphosphorylation of the c-Jun N-terminus activation domain. It also suggests that CD14 is involved in modulating the transactivation potential of c-Jun, which may be associated with the hepatic pathogenesis after injury.