Luckett-Chastain Lerin R, Cottrell Mackenzie L, Kawar Bethany M, Ihnat Michael A, Gallucci Randle M
Pharmaceutical Sciences Department, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
Pharmacotherapy and Experimental Therapeutics Division, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Exp Dermatol. 2017 Aug;26(8):697-704. doi: 10.1111/exd.13260. Epub 2017 Mar 8.
It been shown that IL-6 modulates TGF-β1 expression in fibroblasts, however, what role IL-6 plays concerning TGF-βR expression and function in skin is unknown. Therefore, the aim of this study was to investigate the mechanism by which IL-6 might modulates TGF-β receptors in skin. Skin from WT, IL-6 over-expressing mice and IL-6 treated keratinocyte cultures was analysed for TGF-βRI and TGF-βRII expression via histology, PCR and flow cytometry. Receptor function was assessed by cell migration, bromodeoxyuridine (BrdU) proliferation assays, and Smad7 expression and Smad2/3 phosphorylation. Receptor localization within the membrane was determined by co-immunoprecipitation. IL-6 overexpression and treatment increased TGF-βRII expression in the epidermis. IL-6 treatment of keratinocytes induced TGF-βRI and II expression and augmented TGF-β1-induced function as demonstrated through increased migration and decreased proliferation. Additionally, IL-6 treatment of keratinocytes altered receptor activity as indicated by altered Smad2/3 phosphorylation and increased Smad7 and membrane localization. These results suggest that IL-6 regulates keratinocyte function by modulating TGF-βRI and II expression and signal transduction via trafficking of the receptor to lipid raft pools.
已有研究表明，白细胞介素-6（IL-6）可调节成纤维细胞中转化生长因子-β1（TGF-β1）的表达，然而，IL-6在皮肤中对TGF-β受体表达和功能所起的作用尚不清楚。因此，本研究的目的是探讨IL-6调节皮肤中TGF-β受体的机制。通过组织学、聚合酶链反应（PCR）和流式细胞术分析野生型（WT）小鼠、IL-6过表达小鼠的皮肤以及经IL-6处理的角质形成细胞培养物中TGF-βRI和TGF-βRII的表达。通过细胞迁移、溴脱氧尿苷（BrdU）增殖试验、Smad7表达以及Smad2/3磷酸化来评估受体功能。通过免疫共沉淀确定受体在膜内的定位。IL-6过表达和处理可增加表皮中TGF-βRII的表达。对角质形成细胞进行IL-6处理可诱导TGF-βRI和II的表达，并增强TGF-β1诱导的功能，这通过迁移增加和增殖减少得以证明。此外，对角质形成细胞进行IL-6处理可改变受体活性，表现为Smad2/3磷酸化改变、Smad7增加以及膜定位改变。这些结果表明，IL-6通过调节TGF-βRI和II的表达以及通过将受体转运至脂筏池来调节信号转导，从而调控角质形成细胞的功能。
