Choi Jun-Pyo, Losol Purevsuren, Ayoub Ghazal, Ji Mihong, Kim Sae-Hoon, Cho Sang-Heon, Chang Yoon-Seok
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.
Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, Korea.
Immune Netw. 2022 Apr 15;22(2):e15. doi: 10.4110/in.2022.22.e15. eCollection 2022 Apr.
Foreign molecules, including viruses and bacteria-derived toxins, can also induce airway inflammation. However, to the best of our knowledge, the roles of these molecules in the development of airway inflammation have not been fully elucidated. Herein, we investigated the precise role and synergistic effect of virus-mimicking double-stranded RNA (dsRNA) and staphylococcal enterotoxin B (SEB) in macrophages and epithelial cells. To identify cytokine expression profiles, both the THP-1-derived macrophages and BEAS-2B epithelial cells were stimulated with dsRNA or SEB. A total of 21 cytokines were evaluated in the culture supernatants. We observed that stimulation with dsRNA induced cytokine production in both cell types. However, cytokine production was not induced in SEB-stimulated epithelial cells, compared to the macrophages. The synergistic effect of dsRNA and SEB was evaluated observing cytokine level and intracellular phospho-signaling. Fifteen different types were detected in high-dose dsRNA-stimulated epithelial cells, and 12 distinct types were detected in macrophages; those found in macrophages lacked interferon production compared to the epithelial cells. Notably, a synergistic effect of cytokine induction by co-stimulation of dsRNA and SEB was observed mainly in epithelial cells, via activation of most intracellular phosphor-signaling. However, macrophages only showed an accumulative effect. This study showed that the type and severity of cytokine productions from the epithelium or macrophages could be affected by different intensities and a combination of dsRNA and SEB. Further studies with this approach may improve our understanding of the development and exacerbation of airway inflammation and asthma.
包括病毒和细菌衍生毒素在内的外来分子也可诱发气道炎症。然而，据我们所知，这些分子在气道炎症发展中的作用尚未完全阐明。在此，我们研究了病毒模拟双链RNA（dsRNA）和葡萄球菌肠毒素B（SEB）在巨噬细胞和上皮细胞中的精确作用及协同效应。为了确定细胞因子表达谱，用dsRNA或SEB刺激THP-1来源的巨噬细胞和BEAS-2B上皮细胞。对培养上清液中的21种细胞因子进行了评估。我们观察到，dsRNA刺激可诱导两种细胞类型产生细胞因子。然而，与巨噬细胞相比，SEB刺激的上皮细胞未诱导产生细胞因子。通过观察细胞因子水平和细胞内磷酸信号来评估dsRNA和SEB的协同效应。在高剂量dsRNA刺激的上皮细胞中检测到15种不同类型，在巨噬细胞中检测到12种不同类型；与上皮细胞相比，巨噬细胞中未检测到干扰素产生。值得注意的是，dsRNA和SEB共同刺激诱导细胞因子的协同效应主要在上皮细胞中观察到，这是通过激活大多数细胞内磷酸信号实现的。然而，巨噬细胞仅表现出累加效应。本研究表明，上皮细胞或巨噬细胞产生细胞因子的类型和严重程度可能受到dsRNA和SEB不同强度及组合的影响。采用这种方法的进一步研究可能会增进我们对气道炎症和哮喘发展及加重的理解。
