Yoshimura Shunsuke, Nakamura Hideki, Horai Yoshiro, Nakajima Hideki, Shiraishi Hirokazu, Hayashi Tomayoshi, Takahashi Toshiyuki, Kawakami Atsushi
a Unit of Translational Medicine, Department of Clinical Neuroscience and Neurology , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan .
b Unit of Translational Medicine, Department of Immunology and Rheumatology , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan .
Mod Rheumatol. 2016;26(3):384-90. doi: 10.3109/14397595.2015.1083146. Epub 2016 Mar 29.
To investigate whether aquaporins (AQPs) are involved in salivary gland dysfunction in patients with neuromyelitis optica (NMO) complicated with Sjögren's syndrome (SS).
Eight primary SS (pSS) patients, four NMO spectrum disorder (NMOsd) patients complicated with SS (NMOsd-SS), and three control subjects were enrolled. Immunohistochemistry of labial salivary glands (LSGs) was performed to determine the expressions of AQP4, AQP5, and tumor necrosis factor-alpha (TNF-α). In vitro expression of AQP5 was examined by Western blotting in cultured primary salivary gland epithelial cells (SGECs).
No expression of AQP4 was shown in all LSGs. AQP5 was clearly expressed in the all acini, but the predominant localization of AQP5 in the apical side was diminished in the patients with pSS or NMOsd-SS compared with the controls and tended to be even lower in NMOsd-SS than pSS. The abnormal localization of AQP5 was associated with poor saliva secretion. No difference was found in TNF-α expression in the LSGs between patients with pSS and NMOsd-SS. AQP5 expression of SGECs in vitro was not changed by TNF-α or interleukin-10.
Our results suggest that AQP5 but not AQP4 contributes to salivary secretion in patients with SS including those with NMO complicated with SS.
探讨水通道蛋白(AQPs)是否参与视神经脊髓炎(NMO)合并干燥综合征(SS)患者的唾液腺功能障碍。
纳入8例原发性干燥综合征(pSS)患者、4例合并SS的视神经脊髓炎谱系障碍(NMOsd)患者(NMOsd-SS)及3例对照者。对唇腺(LSGs)进行免疫组织化学检测,以确定水通道蛋白4(AQP4)、水通道蛋白5(AQP5)和肿瘤坏死因子-α(TNF-α)的表达。通过蛋白质免疫印迹法检测原代培养的唾液腺上皮细胞(SGECs)中AQP5的体外表达。
所有唇腺均未显示AQP4表达。AQP5在所有腺泡中均有明显表达,但与对照组相比,pSS或NMOsd-SS患者中AQP5在顶端侧的主要定位减少,且NMOsd-SS患者中的定位比pSS患者更低。AQP5的异常定位与唾液分泌减少有关。pSS患者和NMOsd-SS患者唇腺中TNF-α表达无差异。体外培养的SGECs中AQP5的表达不受TNF-α或白细胞介素-10的影响。
我们的结果表明,AQP5而非AQP4在包括NMO合并SS的SS患者的唾液分泌中起作用。