Induction of corticosteroid insensitivity in human PBMCs by microbial superantigens
Induction of corticosteroid insensitivity in human PBMCs by microbial superantigens
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DOI：
10.1067/mai.2000.105807
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发表时间：
2000-04-01
影响因子：
14.2
通讯作者：
Leung, DYM
中科院分区：
文献类型：
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作者：
Hauk, PJ;Hamid, QA;Leung, DYM
背景资料：微生物超抗原已被描述为有助于慢性炎性疾病的发病机制，通常并发糖皮质激素治疗不敏感。在支气管哮喘中，糖皮质激素不敏感性与糖皮质激素受体β（经典糖皮质激素受体β的内源性抑制剂）的表达增加有关。目的：为了研究超抗原可能导致疾病控制不良的潜在机制，我们检测了它们改变糖皮质激素受体β的类固醇敏感性和表达的能力。方法：测试了地塞米松抑制来自7名健康受试者的PBMC与原型超抗原葡萄球菌肠毒素（SE）β、中毒性休克综合征毒素（TSST）-1和SEE相比PHA刺激的能力。通过免疫细胞化学评估SEE与PHA刺激后正常PBMC中糖皮质激素受体β的表达。地塞米松10（-6）mol/L对PNA诱导的PBMC增殖抑制率为99%，对SE诱导的PBMC增殖抑制率为19%，对TSST-1抑制率为26%，和29%的抑制SE诱导的PBMC增殖（所有超抗原与PHA相比P <0.01），表明超抗原可诱导类固醇不敏感性。SEE刺激正常PBMCs后，其糖皮质激素受体（β）的表达明显高于PHA和未刺激的PBMCs（P <0.01）。结论：微生物超抗原具有诱导糖皮质激素不敏感的能力，在超抗原触发疾病的诊断和治疗中应予以考虑。这些数据表明，超抗原可能通过诱导糖皮质激素受体β导致糖皮质激素不敏感。
Background: Microbial superantigens have been described to contribute to the pathogenesis of chronic inflammatory diseases often complicated by insensitivity to glucocorticoid therapy. In bronchial asthma glucocorticoid insensitivity has been associated with increased expression of glucocorticoid receptor beta, an endogenous inhibitor of the classic glucocorticoid receptor beta.Objective: To study a potential mechanism by which superantigens could contribute to poor disease control, we examined their capacity to alter steroid sensitivity and expression of glucocorticoid receptor beta.Methods: The capacity of dexamethasone to inhibit stimulation of PBMCs from 7 healthy subjects with the prototypic superantigens, staphylococcal enterotoxin (SE) beta, toxic shock syndrome toxin (TSST)-1 and SEE, versus PHA, was tested. The expression of glucocorticoid receptor beta in normal PBMCs after stimulation with SEE, versus PHA, was assessed by immunocytochemistry.Results: Dexamethasone 10(-6) mol/L caused a 99% inhibition of PNA-induced PBMC proliferation but only a 19% inhibition of the SEE-induced, 26% inhibition of the TSST-1, and 29% inhibition of the SEE-induced PBMC proliferation (P < .01 for all superantigens versus PHA) demonstrating that superantigens can induce steroid insensitivity. Stimulation of normal PBMCs with SEE induced a significant increase of glucocorticoid receptor (beta compared with PHA and unstimulated cells (P < .01).Conclusion: We have demonstrated the capacity of microbial superantigens to induce glucocorticoid insensitivity, which should be considered in the diagnosis and treatment of patients with superantigen-triggered diseases. These data suggest that superantigens may contribute to glucocorticoid insensitivity through induction of glucocorticoid receptor beta.