Title

 

Authors

E. Vegeto and A. Maggi

Department of Pharmacological Sciences, University of Milan, Italy

 

Abstract

Estrogens are pleiotropic hormones that act through the interaction with intracellular receptor, ERaand ERb, which are ligand-dependent transcription factors expressed in several tissues and cell lineages. Clinical evidence suggests that a decrease in the levels of circulating estrogens, as it occurs in women at menopause, is associated with a higher incidence of inflammatory disorders; accordingly, estrogens administration correlates with a protective effect against inflammatory pathologies. We thus hypothesized that estrogens exert beneficial effects by acting as anti-inflammatory agents. Using an experimental models of acute inflammation in brain and lung, we demonstrated that 17beta-estradiol reduces the activation and expression of inflammatory genes by inflammatory cells in vivo and that this effect is specifically mediated by ERa (Vegeto et al, 2003, Vegeto et al, 2010). Interestingly, lack of ERa resulted in increased expression of Mac-1 integrin (aMb2, also known as C3R), which has recently been involved in the detrimental effects of microglia  reactivity in experimental models of neurodegenerative pathologies, such as Parkinson’s and Alzheimer’s diseases. We thus tried to manipulate estrogen signaling pathway in macrophages to evaluate its role in the physiology and reactivity of these cells in response to activating stimuli. Our ERs expression data show that different types of resident macrophage cells express ERa and ERbat different levels. Focusing on peritoneal macrophages, we observed that cells obtained from wt or ERa-KO mice display a different morphology, adhesion properties and expression of Mac-1 integrin, thus demonstrating that ERaexpression regulates cell reactivity and that this receptor is somehow involved in Mac-1 activity. Further studies on the interaction between ERaand Mac-1 and on the underlying will be discussed