CD14-and toll-like receptor 4-dependent regulation of c-Fos, c-Jun and c-Jun phosphorylation in the adrenal gland after burn injury

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. Copyright (C) 2004 S. Karger AG, Basel.