Phospholipase A2-dependent release of inflammatory cytokines by superantigen-stimulated nasal polyps of patients with chronic rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is an inflammatory/allergic disease with unclear pathophysiology, but it has been linked to an imbalance in the production of eicosanoids, which are metabolites of arachidonic acid, and results from phospholipids hydrolysis by phospholipase A(2) (PLA(2)). As of yet, the role of PLA(2) in CRS has hardly been studied, except for a report that group II PLA(2) expression is elevated in interleukin (IL) 1 beta or tumor necrosis factor alpha-stimulated CRS nasal tissues with and without polyps. The PLA(2) families include extracellular (secretory) and intracellular isoforms, which are involved in the regulation of inflammatory processes in different ways. Here we comprehensively investigated the expression of PLA(2)s, particularly those reported to be involved in respiratory disorders, in superantigen (SAE)-stimulated nasal polyps from patients with CRS with polyps, and determined their role in inflammatory cytokine production by inhibition of PLA(2) expression. Methods: The release of IL-5, IL-13, IL-17, and interferon gamma by nasal polyps dispersed cells (NPDC) was determined concomitantly with PLA(2) messenger RNA expression, under SAE stimulation, with or without dexamethasone, as a regulator of PLA(2) expression. Results: Stimulation of NPDCs by SAE-induced cytokine secretion with enhanced expression of several secretory PLA(2) and Ca2+-independent PLA(2), while suppressing cytosolic PLA(2) expression. All these were reverted to the level of unstimulated NPDCs on treatment with dexamethasone. Conclusion: This study further supports the key role of secretory PLA(2) in the pathophysiology of respiratory disorders and presents secretory PLA(2) inhibition as a therapeutic strategy for the treatment of CRS and airway pathologies in general.