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

Abstract

Introduction: 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 the lipopolysaccharide (LPS)-mediated sepsis, we examined the involvement of the LPS signaling pathway in the regulation of these transcription factors utilizing CD14 knockout and toll-like receptor 4 mutant mice. Methods: CD14 knockout, toll-like receptor 4 (TLR4) mutant, and their respective wild type mice were subjected to 18% total surface area burn. Their adrenal glands were harvested and analyzed for c-Jun and c-Fos mRNA and protein expression using RT-PCR and Western blot methods. Results: There was a rapid induction of c-Jun and c-Fos expression (mRNA and protein), as well as c-Jun serine phosphorylation. The induction of c-Jun and its phosphorylation after injury was greater in CD14 knockout and TLR4 mutant mice compared to their respective wild types. A similar pattern was observed in the c-Fos response. Conclusions: These data suggest that c-Fos and c-Jun are activated in the adrenal gland in response to burn injury. In addition, a LPS-mediated signaling pathway may inhibit the induction of these transcription factors after injury.