Rhinitis, sinusitis, and upper airway disease
Staphylococcus aureus enterotoxin B, protein A, and lipoteichoic acid stimulations in nasal polyps

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Background

Increasing evidence points toward a modifying role of Staphylococcus aureus and its products in the pathogenesis of nasal polyposis.

Objective

The aim of this study was to investigate cytokine and mediator production after stimulation with S aureus–derived proteins enterotoxin B, protein A, and lipoteichoic acid in nasal polyp and control inferior turbinate tissue.

Methods

Tissue fragments were stimulated with RPMI (negative control), enterotoxin B, protein A, and lipoteichoic acid for 30 minutes and 24 hours. Supernatants were measured by multiplex for proinflammatory cytokines (IL-1β, TNF-α) and T-cell and subset–related cytokines (IFN-γ, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13). Histamine, TGF-β1, cysteinyl leukotrienes, and prostaglandin D2 were analyzed by ELISA.

Results

Thirty minutes of protein A stimulation resulted in a significant increase of histamine, leukotrienes, and prostaglandin D2. Enterotoxin B stimulation over a period of 24 hours induced a significant increase of IL-1β, TNF-α, IFN-γ, IL-2, IL-4, IL-5, IL-10, and IL-13 in both groups, with this increase significantly higher in nasal polyps compared with controls.

Conclusion

We here show that S aureus products have various effects on mucosal tissues: surface protein A induces mast cell degranulation, whereas enterotoxins induce the release of cytokines, with a TH2-skewed pattern in nasal polyps, supporting the stimulatory role of superantigens in the development of this inflammatory disease.

Section snippets

Patients

Nasal tissue was obtained from 25 patients at the Department of Otorhinolaryngology of the Ghent University Hospital. The ethical committee of the Ghent University Hospital approved the study, and all patients gave their written informed consent before inclusion in the study. None of the subjects received intranasal corticosteroids, antihistamines, antileukotrienes, oral and intranasal decongestants, or intranasal anticholinergics within 1 week before surgery, and none of the subjects received

SEB stimulations

The inferior turbinates (n = 13) and the nasal polyp explants (n = 12) were stimulated for 30 minutes and for 24 hours with culture medium alone (RPMI) and SEB (0.5 μg/mL). SEB stimulation for 30 minutes did not increase the release of cytokines in comparison with culture medium alone in controls or NP (results not shown).

Twenty-four–hour SEB stimulation demonstrated a significant increase of TH1 and TH2 cytokines (IFN-γ, IL-2, IL-4, IL-5, IL-10, and IL-13) in inferior turbinates and NP

Discussion

We show here that staphylococcal products have different effects on nasal mucosal samples: SpA after 30 minutes resulted in the early release of mast cell mediators including histamine, LTC4/D4/E4, and PGD2, whereas SEB after 24 hours induced a late-phase release of numerous immunoregulatory and proinflammatory cytokines, favoring TH2 cytokines and disfavoring IL-10 and TGF-β1 in nasal polyps.

There is increasing evidence that the colonization of S aureus and the release of its cell products may

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    Supported by a grant from the Flemish Scientific Research Board, Fonds voor Wetenschappelijk Onderzoek, no. A12/5-K/V-K17 to C.B.; by a postdoctoral grant of the Research Foundation-Flanders (FWO) to P.G.; by a grant from the research funds of Ghent University (Bijzonder Onderzoeksfonds) to T.V.Z.; and by an unrestricted research grant from GlaxoSmithKline, Stevenage, United Kingdom.

    Disclosure of potential conflict of interest: J. Patou has received grant support from GlaxoSmithKline. The rest of the authors have declared that they have no conflict of interest.

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