Prostanoids actions in inflammatory processes

Pathophysiology and Therapy of Immune and Inflammatory Diseases
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)

Unsaturated fatty acids are metabolized to reactive products that play an essential role in a variety of pathophysiological processes. The enzymatic oxygenation of these fatty acids generates autocrine and paracrine signaling mediators as those of the eicosanoids lipid family, that includes prostaglandins and leukotrienes. Current knowledge indicates that these enzymatically oxidized unsaturated fatty acid-derived products are important signalling molecules in an array of physiological processes as vascular and renal homeostasis, cellular growth and differentiation. Under pathological conditions, prostanoids are central for the development of inflammatory reactions being regarded as critical mediators in a variety of severe diseases such as arthritis, atherosclerosis and cancer. Among the different prostaglandins subtypes, our current research is focused on a class of electrophilic compounds named cyclopentenones (CyPGs) which play an important role in the inflammatory process acting as anti-inflammatory pro-resolving agents.

Electrophilic fatty acid species also include nitro-containing fatty acids as nitroalkene derivatives of linoleic acid and oleic acid (LNO2 and OA-NO2). These compounds are a novel class of endogenous, electrophilic mediators that can also exert adaptive anti-inflammatory signalling reactions.

Electrophilic oxo or nitro fatty acids can modulate the activation, differentiation and function of different cell types as those involved in the inflammatory process and the immune response. These effects occur due to their ability to covalently modify transcriptional regulatory proteins and enzymes and to activate various nuclear and membrane receptors, finally modifying protein function and altering patterns of gene expression.

Our investigations are aimed to the study of the molecular mechanisms involved in the actions displayed by bioactive electrophilic fatty acids such as cyclopentenones or nitro fatty acids, as modulators of inflammation and the immune response. To this end, we analyze their influence on diverse parameters of macrophages and T lymphocytes function, focusing on their effects on transcriptional activation and gene expression and their consequences on cell activation and differentiation.

Research on the molecular and cellular basis of the actions of electrophilic fatty acids in inflammation and the immune response is required to clearly understand the potential benefits and risks of pharmaceutical intervention with these lipids in the onset and progress of inflammatory diseases.

Biomolecules & Cell D.
Molecular Biomedicine
Miguel Ángel Íñiguez