Endocrine influence on neuroinflammation: the use of reporter systems

Abstract

Most of the ageing-associated pathologies are coupled with a strong inflammatory component that accelerates the progress of the physio-pathological functional decline related to ageing. The currently available pharmacological tools for the control of neuroinflammation present several side effects which restrict their application, particularly in chronic disorders. The discovery of the potential anti-inflammatory action exerted by endogenous estrogens and that activation of ERα results in a significant decrease of inflammation at the cellular level and in models of inflammatory diseases, prompted us to embark in a series of studies aimed at the generation of reporter systems allowing to i.) understand the anti-inflammatory action of estrogens at molecular level, ii.) evaluate the extent to which the action of this steroid hormone was relevant in models of pathologies characterized by a strong inflammatory component and iii.) investigate the efficacy of novel, synthetic estrogens endowed of anti-inflammatory activity. To this aim, we conceived the NFkB-luc2 reporter mouse, a model characterized by dual reporter genes for fluorescence and bioluminescence imaging under the control of a synthetic DNA able to bind the transcription factor (TF) NFkB, the master regulator of the expression of most of the cytokines responsible for the initial phase of acute inflammation. We here summarize the philosophy that has driven our research in the past years and some of the results obtained so far.

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