Department of Otorhinolaryngology and Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Science, Hiroshima University, Minami-ku, Hiroshima, Japan.
Rhinology. 2009 Dec;47(4):413-8. doi: 10.4193/Rhin08.074.
The aim of this study was to examine the innate immune response induced by toll-like receptors (TLRs) in the paranasal sinus epithelial cells in cell culture models and to examine the effect of glucocorticoids (GCs) on the innate immune response.
After stimulation with lipopolysaccharide (LPS) and peptidoglycan (PGN), p50 level was measured as an index of the innate response in the paranasal sinus epithelium. To observe the effect of GCs, the specimens were pre-treated with dexamethasone (DEX) for 48 hours prior to stimulation. On immunocytochemistry GR, TLR2 and TLR4 in the paranasal sinus epithelium were observed.
The p50 activity levels increased after stimulation with LPS and PGN in a dose-dependent manner. Pretreatment with DEX significantly suppressed the increase in p50 activity levels induced by LPS and PGN. On immunocytochemistry, TLR2 and TLR4 immunoreactivities were relatively high after 48h DEX pretreatment.
The increase in NF-kappaB activity after LPS and PGN stimulation suggests that stimulation through TLR2 and TLR4 may induce high cytokine expression and inflammatory cell migration in the paranasal sinus epithelial cells. In paranasal sinus epithelial cells GCs not only have anti-inflammatory effects through transcription factor inhibition but also enhance innate host defences.
本研究旨在探讨细胞培养模型中鼻旁窦上皮细胞 Toll 样受体(TLR)诱导的固有免疫反应,并研究糖皮质激素(GCs)对固有免疫反应的影响。
用脂多糖(LPS)和肽聚糖(PGN)刺激后,以 p50 水平作为鼻旁窦上皮固有反应的指标。为了观察 GCs 的作用,在刺激前用地塞米松(DEX)预处理标本 48 小时。用免疫细胞化学法观察鼻旁窦上皮中的 GR、TLR2 和 TLR4。
LPS 和 PGN 刺激后,p50 活性水平呈剂量依赖性增加。DEX 预处理显著抑制了 LPS 和 PGN 诱导的 p50 活性水平的增加。免疫细胞化学染色显示,DEX 预处理 48 小时后 TLR2 和 TLR4 免疫反应性相对较高。
LPS 和 PGN 刺激后 NF-κB 活性的增加表明,TLR2 和 TLR4 的刺激可能导致鼻旁窦上皮细胞中细胞因子表达和炎症细胞迁移增加。在鼻旁窦上皮细胞中,GCs 不仅通过转录因子抑制具有抗炎作用,而且还增强固有宿主防御。