Regulation of Arachidonic Acid Pathway and Eosinophilic Inflammation in Chronic Rhinosinusitis/ Nasal Polyposis. Potential Role of Staphylococcus aureus Enterotoxins

linked to inflammation. Furthermore, EP2 and EP4 receptor expression was increased in chronic rhinosinusitis and nasal polyp subjects in contrast to EP1 and EP3, which were down regulated in the polyp group, suggesting a distinctive role of these receptors in the pathophysiology of nasal polyposis. Finally, based on our previous findings and parallel work of our group, we studied the influence of S. aureus enterotoxins in the regulation of both eosinophilic inflammatory and eicosanoid pathways. We first show that nasal polyposis/aspirin intolerance was associated with increased concentrations of eosinophil-related mediators, as well as of IgE antibodies to S. aureus enterotoxins. Furthermore, eicosanoid release evaluated in nasal polyp patients showed an increase of leukotrienes and lipoxin A4 in patients with immune response - 18 - against S. aureus enterotoxins, which seem to be correlated to the enterotoxin-derived inflammatory reaction and unrelated to asthma and allergy conditions. These findings were extended to structural cells (fibroblasts). These in vitro experiments demonstrated that S. aureus enterotoxin B could regulate the production of PGE2 and influence important cell physiological mechanisms like growth and migration. The results of our studies provide new insights about the molecular interactions and the role of bacterial infection in the regulation of two crucial inflammatory mechanisms operating in airway human diseases, the eicosanoid biosynthetic and the eosinophilic pathway