The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Center for Immunology, Inflammation, & Immune-mediated disease, Guangzhou Medical University, Guangzhou 510260, China.
Center for the Study of Itch, Department of Anesthesiology, Washington University School of Medicine.
Asian Pac J Allergy Immunol. 2020 Mar;38(1):52-63. doi: 10.12932/AP-220818-0396.
Staphylococcal enterotoxin A (SEA) is a well-known superantigen and stimulates human peripheral blood mononuclear cells (PBMCs) involving in the pathogenesis of inflammatory disorders and cancer.
To better understand the biological activities of SEA and the possible intracellular mechanisms by which SEA plays its roles in conditions like staphylococcal inflammatory and/or autoimmune disorders and immunotherapy.
Recombinant SEA (rSEA) was expressed in a prokaryotic expression system and its effects on the cytokine and chemokine production was examined by Enzyme-linked Immunospot (ELISpot) Assay and ELISA analysis.
In vitro experiments showed rSEA could significantly enhance secretion of a broad spectrum of cytokines and chemokines from PBMCs dose-dependently. Increased secretion of cytokines and chemokines from rSEA stimulated PBMCs was barely affected by C-C motif chemokine receptor 2 (CCR2) antagonist INCB3344. However, Src, ERK and STAT pathway inhibitors were able to successfully block the enhanced secretion of most of cytokines and chemokines produced by rSEA stimulated PBMCs.
Our work suggested that rSEA serves as a potent stimulant of PBMCs, and induces the release of cytokines and chemokines through Src, ERK and STAT pathways upon a relatively independent network. Our work also strongly supported that Src, ERK and STAT signaling inhibitors could be effective therapeutic agents against diseases like toxic shock syndrome or infection by microbes resistant to antibiotics.
葡萄球菌肠毒素 A (SEA) 是一种众所周知的超抗原，可刺激人类外周血单核细胞 (PBMC)，参与炎症性疾病和癌症的发病机制。
更好地了解 SEA 的生物学活性，以及 SEA 在葡萄球菌炎症和/或自身免疫性疾病和免疫治疗等情况下发挥作用的可能细胞内机制。
在原核表达系统中表达重组 SEA (rSEA)，并通过酶联免疫斑点 (ELISpot) 分析和 ELISA 分析检测其对细胞因子和趋化因子产生的影响。
体外实验表明，rSEA 可显著增强 PBMC 产生的广泛细胞因子和趋化因子的分泌，呈剂量依赖性。rSEA 刺激 PBMC 产生的细胞因子和趋化因子的分泌几乎不受 C-C 基序趋化因子受体 2 (CCR2) 拮抗剂 INCB3344 的影响。然而，Src、ERK 和 STAT 通路抑制剂能够成功阻断 rSEA 刺激 PBMC 产生的大多数细胞因子和趋化因子的增强分泌。
我们的工作表明，rSEA 是 PBMC 的有效刺激物，通过 Src、ERK 和 STAT 通路在相对独立的网络中诱导细胞因子和趋化因子的释放。我们的工作还强烈支持 Src、ERK 和 STAT 信号通路抑制剂可以成为治疗中毒性休克综合征或对抗生素耐药微生物感染等疾病的有效治疗药物。
