Xu G, Xia J H, Zhou H, Yu C Z, Zhang Y, Zuo K J, Shi J B, Li H B
Allergy and Cancer Center, Otorhinolaryngology Hospital of the First Affiliated Hospital of Sun Yat-sen University, and Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
Clin Exp Allergy. 2009 Jun;39(6):829-37. doi: 10.1111/j.1365-2222.2009.03218.x. Epub 2009 Mar 2.
The pathogenesis of nasal polyps is still unclear. There is increasing evidence indicating that Staphylococcal aureus (S. aureus) is associated with the formation of nasal polyps, but the mechanism has not been well documented to date.
We stimulated cultured nasal polyps and turbinate tissues with Staphylococcal exotoxin B (SEB), detected the expression of pro-inflammatory cytokines (IL-2, IL-6, and IL-8) and T cell cytokines (IFN-gamma, IL-4, IL-5, IL-10, and IL-17) in the supernatants, and evaluated mRNA expression (T-bet, GATA-3, Foxp3, and RORgammat) and frequencies of CD4+CD25+ T regulatory cells (Tregs) in nasal tissues. We also evaluated the effects of blocking IL-6 with monoclonal antibodies to T cell profiles in cultured nasal tissues stimulated by SEB.
Levels of IL-6, IFN-gamma and IL-4 increased significantly in SEB-stimulated nasal polyps. Meanwhile, mRNA expressions of T-bet and GATA-3 were significantly up-regulated, while Foxp3 was inhibited and the frequencies of CD4+CD25+ Tregs were decreased after SEB stimulation. After blocking IL-6, the levels of IL-10 and Foxp3 mRNA, as well as the frequencies of CD4+CD25+ Tregs, were significantly increased, while IFN-gamma and IL-4 production and the mRNA expression of T-bet and GATA-3 were significantly inhibited.
SEB is able to modulate pro-inflammatory factors, T-helper type 1/Th2 profiles and suppress Treg activity in cultured nasal polyps, which were rescued by blocking IL-6 activity. Therefore, IL-6 is essential for SEB-induced Treg insufficiency in nasal polyps.
鼻息肉的发病机制仍不清楚。越来越多的证据表明金黄色葡萄球菌（S. aureus）与鼻息肉的形成有关，但迄今为止其机制尚未得到充分记录。
我们用葡萄球菌外毒素B（SEB）刺激培养的鼻息肉和鼻甲组织，检测上清液中促炎细胞因子（IL-2、IL-6和IL-8）和T细胞细胞因子（IFN-γ、IL-4、IL-5、IL-10和IL-17）的表达，并评估鼻组织中mRNA表达（T-bet、GATA-3、Foxp3和RORgammat）以及CD4+CD25+调节性T细胞（Tregs）的频率。我们还用单克隆抗体阻断IL-6，评估其对SEB刺激的培养鼻组织中T细胞谱的影响。
在SEB刺激的鼻息肉中，IL-6、IFN-γ和IL-4水平显著升高。同时，SEB刺激后，T-bet和GATA-3的mRNA表达显著上调，而Foxp3受到抑制，CD4+CD25+ Tregs的频率降低。阻断IL-6后，IL-10和Foxp3 mRNA水平以及CD4+CD25+ Tregs的频率显著增加，而IFN-γ和IL-4的产生以及T-bet和GATA-3的mRNA表达显著受到抑制。
SEB能够调节培养的鼻息肉中的促炎因子、辅助性T细胞1/Th2谱并抑制Treg活性，而阻断IL-6活性可挽救这些作用。因此，IL-6对于SEB诱导的鼻息肉中Treg功能不全至关重要。
