Background: Chronic rhinosinusitis (CRS) is an inflammatory/allergic disease with unclear pathophysiology, but it has been linkd to an imbalance in the production ofeicosanoids, which are metabolites of arachidonic acid, and results from phospholipids hydrolysis by phospholipase PLA2). As of yet, the role of PLA2 in CRS has hardly been studied, except for a report that group II PLA2 expression is elevated in interleukin (IL) 1β or tumor necrosis factor α-stimulated CRS nasal tissues with and without polyps. The PLA2 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 PLA2s, 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 PLA2 expression. Methods: The release of IL-5, IL-13, IL-17, and interferon γ by nasal polyps dispersed cell NPDC) was determined concomitantly with PLA2 messenger RNA expression, under SAE stimulation, with or without dexamethasone, as a regulator of PLA2 expression. Results: Stimulation of NPDCs by SAE-induced cytokine secretion with enhanced expression of several s tory PLA2 and Ca2+-independent PLA2, while suppressing cytosolic PLA2 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 PLA2 in the pathophysiology of respiratory disorders and presents secretory PLA2 inhibition as a therapeutic strategy for the treatment of CRS and airway pathologies in general.