Study of anti-inflammatory and proinflammatory proteins as possible therapeutic targets in experimental models of neuroinflammation and cutaneous inflammation

Abstract

In the last years, the research by our group has been focused the role of proteins with anti and proinflammatory activities, specially the galectins-1, -3 and annexin A1 (ANXA1), using different experimental models of inflammation. Thus, these investigations have been expanded with a dual approach: 1) on one hand, the patho-physiological relevance of these mediators in different models of inflammation is determined using a combination of histopathology, pharmacological and ultrastructural analysis; 2) on the other hand, an equally important goal is identification of the targets mediating the effects of endogenous anti-inflammation as novel leads for innovative drug discovery: these new therapeutics will potentially produce much less side effects. ANXA1 and galectins act as potent endogenous mediators in inflammation capable of controlling the process of leukocyte transmigration, cytokine release and mast cell degranulation, thus contributing to the homeostasis of the inflammatory reaction. However, the molecular mechanisms by which these proteins modulate cellular responses, particularly in neuroinflammation and cutaneous inflammations, are not yet fully determined. Epilepsy is a brain disorder caused by the permanent predisposition of the brain to generate spontaneous and recurrent epileptic seizures, accompanied by neurobiological, cognitive and social consequences. Clinical and experimental evidence indicates that the inflammatory process in the brain is a crucial mechanism in the pathophysiology of epileptic seizures and epilepsy, arousing interest in the use of anti-inflammatory drugs. We also emphasize that immune responses involving chronic inflammations of the skin, such as psoriasis and dermatitis, are complex and evidence the challenge in clinical diagnosis, and it is fundamental to study biomarkers to better define these pathologies, which will contribute to a more personalized therapy. In the treatment of inflammatory diseases, in general, glucocorticoids and immunosuppressants are the drugs administered whose adverse effects stimulate studies for new therapeutic strategies. Thus, we will evaluate the expression and mechanism of action of the ANXA1 and galectin proteins in experimental models of neuroinflammation and cutaneous inflammations. Different methodologies will be used, such as: histological analysis and quantification of inflammatory cells, immunohistochemistry, immunofluorescence, Elisa, western blotting, etc, that will enable a detailed understanding of the bioactivity of proteins and their possible therapeutic applications. (AU)