Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, South Korea.
Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, South Korea.
Cytokine. 2020 Jan;125:154798. doi: 10.1016/j.cyto.2019.154798. Epub 2019 Aug 17.
IL-36 family, a recently reported member of the IL-1 cytokine family, plays an essential role in nonspecific innate immune response to infection. This study aims at investigating the expression of IL-36 family members (α, β, and γ) in normal and inflammatory sinus mucosa of patients with chronic rhinosinusitis (CRS), their effects on chemokine secretion and on the barrier function of epithelial and endothelial cells, and the effect of Toll-like receptors on the expression of IL-36 in epithelial cells.
The expression of IL-36 family in normal and inflammatory sinus mucosa, the production of chemokines or the expression levels of IL-36 family in epithelial cells treated with IL-36 family members or stimulated with TLR3, TLR4, TLR5, or TLR7/8 agonists were measured with real time PCR, ELISA, immunohistochemistry, or Western blot. The epithelial and endothelial permeability, and transendothelial leukocyte migration were investigated using cultured epithelial and endothelial cells.
IL-36α, IL-36β, and IL-36γ were localized in epithelial cells of sinonasal mucosa. Their levels increased in inflammatory mucosa of CRS patients and are up-regulated by TLR3, TLR4, or TLR5 agonists. IL-36α, or IL-36γ induced CXCL1, CXCL2, and CXCL3 production. Epithelial and endothelial permeability, transendothelial leukocyte migration were increased in cells treated with IL-36α, IL-36β, or IL-36γ.
These results suggest that IL-36α, IL-36β, and IL-36γ localized in superficial epithelium may act as a responder to microbial and nonmicrobial elements through TLR and subsequently produce CXC chemokines, playing an interplay between innate and adaptive immune response.
IL-36 家族是最近报道的 IL-1 细胞因子家族的一个成员，在感染引起的非特异性先天免疫反应中发挥重要作用。本研究旨在探讨 IL-36 家族成员（α、β 和 γ）在慢性鼻-鼻窦炎（CRS）患者正常和炎症鼻窦黏膜中的表达，它们对趋化因子分泌以及上皮细胞和内皮细胞屏障功能的影响，以及 Toll 样受体（TLR）对上皮细胞中 IL-36 表达的影响。
采用实时 PCR、ELISA、免疫组织化学或 Western blot 检测正常和炎症鼻窦黏膜中 IL-36 家族的表达，用 IL-36 家族成员或 TLR3、TLR4、TLR5 或 TLR7/8 激动剂刺激后上皮细胞产生的趋化因子或 IL-36 家族的表达水平。采用培养的上皮细胞和内皮细胞研究上皮和内皮通透性以及跨内皮白细胞迁移。
IL-36α、IL-36β 和 IL-36γ 定位于鼻-鼻窦黏膜上皮细胞。它们在 CRS 患者炎症性黏膜中的水平增加，并受 TLR3、TLR4 或 TLR5 激动剂上调。IL-36α 或 IL-36γ 诱导 CXCL1、CXCL2 和 CXCL3 的产生。用 IL-36α、IL-36β 或 IL-36γ 处理的细胞，上皮和内皮通透性以及跨内皮白细胞迁移增加。
这些结果表明，定位于浅层上皮的 IL-36α、IL-36β 和 IL-36γ 可能通过 TLR 作为对微生物和非微生物因素的应答者，随后产生 CXC 趋化因子，在先天免疫和适应性免疫反应之间发挥相互作用。
