Nakamura Hideki, Kawakami Atsushi, Ida Hiroaki, Koji Takehiko, Eguchi Katsumi
The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki City, Nagasaki, Japan.
Rheumatol Int. 2007 Dec;28(2):127-36. doi: 10.1007/s00296-007-0411-9. Epub 2007 Jul 20.
Epidermal growth factor (EGF) exerts tropic effects on salivary epithelial cells. We examined EGF-mediated signaling pathways in the salivary epithelial cells of patients with Sjögren's syndrome (SS). We compared the immunohistochemical expression of EGF receptor (EGF-R), phosphatidylinositol 3-kinase (PI3K), Akt and nuclear factor kappa B (NF-kappaB) in the labial salivary glands of SS patients (n = 6) with those of control subjects (n = 2). EGF-mediated signaling pathways were further studied in vitro (n = 3) using primary salivary epithelial cells; NF-kappaB p65 nuclear translocation and Akt phosphorylation were examined by immunofluorescence and western blotting, respectively. The phosphorylation of EGF-R and Akt, and the nuclear expression of NF-kappaB p65, were increased in situ in the salivary epithelial cells of SS patients compared with those of control subjects. Epidermal growth factor induced rapid EGF-R phosphorylation and NF-kappaB p65 nuclear translocation in primary salivary epithelial cells in vitro. However, EGF also induced late Akt phosphorylation (after 12 h). Chemical inhibition of PI3K-Akt by LY294002/wortmannin did not affect EGF-mediated NF-kappaB p65 nuclear translocation; and NF-kappaB inhibition by Bay 11-7082 did not suppress Akt phosphorylation. Our data suggest that EGF stimulates both the PI3K-Akt pathway and NF-kappaB via distinct mechanisms, promoting tropic effects in SS salivary epithelial cells.
表皮生长因子（EGF）对唾液上皮细胞具有促生长作用。我们研究了干燥综合征（SS）患者唾液上皮细胞中EGF介导的信号通路。我们比较了SS患者（n = 6）与对照受试者（n = 2）唇腺中表皮生长因子受体（EGF-R）、磷脂酰肌醇3-激酶（PI3K）、Akt和核因子κB（NF-κB）的免疫组化表达。使用原代唾液上皮细胞在体外（n = 3）进一步研究EGF介导的信号通路；分别通过免疫荧光和蛋白质印迹检测NF-κB p65核转位和Akt磷酸化。与对照受试者相比，SS患者唾液上皮细胞中EGF-R和Akt的磷酸化以及NF-κB p65的核表达在原位增加。在体外原代唾液上皮细胞中，表皮生长因子诱导EGF-R快速磷酸化和NF-κB p65核转位。然而，EGF也诱导晚期Akt磷酸化（12小时后）。LY294002/渥曼青霉素对PI3K-Akt的化学抑制不影响EGF介导的NF-κB p65核转位；Bay 11-7082对NF-κB的抑制不抑制Akt磷酸化。我们的数据表明，EGF通过不同机制刺激PI3K-Akt途径和NF-κB，促进SS唾液上皮细胞的促生长作用。
