Phospholipase A2-dependent Release of Inflammatory Cytokines by Superantigen-Stimulated Nasal Polyps of Patients with Chronic Rhinosinusitis

Abstract

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 A₂ (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 cells (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 secretory 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.