CD14- and Toll-Like Receptor 4-Dependent Regulation of c-Fos, c-Jun and c-Jun Phosphorylation in the Adrenal Gland afterBurn Injury

Abstract

Objectives: Although the pathophysiology of the adrenocortical response after injury has been described, alterations in the molecular profile (e.g. transcription factors) of the adrenal gland itself are not well understood. The regulation of c-Fos, c-Jun, and c-Jun phosphorylation in the adrenal gland after burn injury was investigated in this study. In addition, since burn injury is often associated with lipopolysaccharide (LPS)-mediated sepsis, we examined the involvement of the LPS signaling pathway in the regulation of these transcription factors utilizing CD14 knockout and C3H/HeJ (encoding defective toll-like receptor 4) mice. Methods: Adrenal glands harvested after an 18% total body surface area burn were subjected to RT-PCR and Western blot analyses of c-Jun and c-Fos. Results: There was a rapid induction of c-Jun and c-Fos expression (mRNA and protein), and c-Jun serine phosphorylation. The induction of c-Jun and its phosphorylation after injury was greater in CD14 knockout and C3H/HeJ mice compared to their respective controls. A similar pattern was observed in the c-Fos regulation. Conclusions: These data suggest that c-Fos and c-Jun are activated in the adrenal gland in response to burn injury. In addition, an LPS-mediated signaling pathway may influence the regulation of these transcription factors after injury.