TY - JOUR
T1 - Cellular responses to Staphylococcus aureus alpha-toxin in chronic rhinosinusitis with nasal polyps
AU - Okano, Mitsuhiro
AU - Fujiwara, Tazuko
AU - Kariya, Shin
AU - Higaki, Takaya
AU - Haruna, Takenori
AU - Matsushita, Osamu
AU - Noda, Yohei
AU - Makihara, Seiichiro
AU - Kanai, Kengo
AU - Noyama, Yasuyuki
AU - Taniguchi, Masami
AU - Nishizaki, Kazunori
N1 - Funding Information:
The authors would like to thank Dr. Tomomi Miy-atake for their excellent assistance in tissue sampling, and Yuko Okano for her editorial assistance. This work was supported in part by grants from Ministry of Education, Culture, Sports, Science and Technology of Japan (23592511) and Ministry of Health, Labour and Welfare of Japan.
Publisher Copyright:
© 2014 Japanese Society of Allergology.
PY - 2014
Y1 - 2014
N2 - Background: In contrast to Staphylococcus aureus-derived superantigenic exotoxins, the role of nonsuperantigenic exotoxins in the pathogenesis of eosinophilic airway diseases remains obscure. We sought to characterize S. aureus alpha-toxin-induced cellular responses in chronic rhinosinusitis with nasal polyps (CRSwNP).Methods: Dispersed nasal polyp cells and uncinate tissue cells were prepared from patients with CRS with and without nasal polyps, respectively. Cells were incubated with various concentrations of alpha-toxin or staphylococcal enterotoxin B and then the levels of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in the cell supernatants were determined. The pathophysiological significance of alpha-toxin-induced cytokine production was also determined including radiological severity of rhinosinusitis, tissue and blood eosinophilia, serum total IgE level, and 1-s forced expiratory volume[1]forced vital capacity ratio (FEV1/FVC).Results: Nasal polyp cells produced substantial amounts of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in response to alpha-toxin. Cytokine production was higher in nasal polyp cells than in uncinate tissue cells. The potency of alpha-toxin in stimulating IL-5, IL-13, and IL-10 production was comparable to that of enterotoxin. Alpha-toxininduced IFN-γ, IL-17A, and IL-10 production significantly and negatively correlated with the degree of eosinophil infiltration into nasal polyps. Conversely, alpha-toxin-induced IFN-γ and IL-10 production significantly and positively correlated with FEV1/FVC. IL-10 production was significantly lower in asthmatic patients compared to non-asthmaticsConclusions: S. aureus-derived alpha-toxin can provoke cellular responses in nasal polyps. These responses, especially failure to synthesize IL-10, may play a role in the pathophysiology of CRSwNP.
AB - Background: In contrast to Staphylococcus aureus-derived superantigenic exotoxins, the role of nonsuperantigenic exotoxins in the pathogenesis of eosinophilic airway diseases remains obscure. We sought to characterize S. aureus alpha-toxin-induced cellular responses in chronic rhinosinusitis with nasal polyps (CRSwNP).Methods: Dispersed nasal polyp cells and uncinate tissue cells were prepared from patients with CRS with and without nasal polyps, respectively. Cells were incubated with various concentrations of alpha-toxin or staphylococcal enterotoxin B and then the levels of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in the cell supernatants were determined. The pathophysiological significance of alpha-toxin-induced cytokine production was also determined including radiological severity of rhinosinusitis, tissue and blood eosinophilia, serum total IgE level, and 1-s forced expiratory volume[1]forced vital capacity ratio (FEV1/FVC).Results: Nasal polyp cells produced substantial amounts of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in response to alpha-toxin. Cytokine production was higher in nasal polyp cells than in uncinate tissue cells. The potency of alpha-toxin in stimulating IL-5, IL-13, and IL-10 production was comparable to that of enterotoxin. Alpha-toxininduced IFN-γ, IL-17A, and IL-10 production significantly and negatively correlated with the degree of eosinophil infiltration into nasal polyps. Conversely, alpha-toxin-induced IFN-γ and IL-10 production significantly and positively correlated with FEV1/FVC. IL-10 production was significantly lower in asthmatic patients compared to non-asthmaticsConclusions: S. aureus-derived alpha-toxin can provoke cellular responses in nasal polyps. These responses, especially failure to synthesize IL-10, may play a role in the pathophysiology of CRSwNP.
KW - Alpha-toxin
KW - Chronic rhinosinusitis
KW - Eosinophil
KW - IL-10
KW - Nasal polyps
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U2 - 10.2332/allergolint.14-OA-0703
DO - 10.2332/allergolint.14-OA-0703
M3 - Article
C2 - 25056228
AN - SCOPUS:84924806512
VL - 63
SP - 563
EP - 573
JO - Allergology International
JF - Allergology International
SN - 1323-8930
IS - 4
ER -