Wada Makoto, Kawahito Yutaka, Kimura Shinya, Kohno Masataka, Ishino Hidetaka, Kimura Mizuho, Omoto Atsushi, Yamamoto Aihiro, Hamaguchi Masahide, Tsubouchi Yasunori, Tokunaga Daisaku, Hojo Tatsuya, Ashihara Eishi, Maekawa Taira, Yoshikawa Toshikazu
Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Biochem Biophys Res Commun. 2007 Jun 1;357(2):353-9. doi: 10.1016/j.bbrc.2007.03.190. Epub 2007 Apr 9.
Polo-like kinase-1 (PLK-1) is a member of the PLK family and participates in the control of cell mitosis. Here, we show that immunoreactive PLK-1 is strongly expressed in synoviocytes and some infiltrative mononuclear cells in synovial tissues from patients with rheumatoid arthritis (RA), while patients with osteoarthritis and injury show little or no expression of PLK-1 in synovial tissues. Western blot analysis shows that PLK is expressed and its expression is enhanced by IL-1beta in RA synoviocytes. IL-1beta also enhanced the cell growth of RA synoviocytes. Moreover, siRNA targeted against PLK-1 significantly decreases the expression of PLK-1 of RA synoviocytes stimulated by IL-1beta and suppresses the proliferation of these synoviocytes through apoptosis. These findings suggest that PLK-1 plays a critical role in the proliferation of RA synoviocytes leading to bone destruction, and siRNA against PLK-1 is potentially useful for the treatment of RA.
Polo样激酶1(PLK-1)是PLK家族的成员之一,参与细胞有丝分裂的调控。在此,我们发现,类风湿关节炎(RA)患者滑膜组织中的滑膜细胞和一些浸润性单核细胞中强烈表达免疫反应性PLK-1,而骨关节炎和损伤患者的滑膜组织中PLK-1表达很少或无表达。蛋白质免疫印迹分析表明,RA滑膜细胞中表达PLK,且白细胞介素-1β(IL-1β)可增强其表达。IL-1β还可促进RA滑膜细胞的生长。此外,靶向PLK-1的小干扰RNA(siRNA)可显著降低IL-1β刺激的RA滑膜细胞中PLK-1的表达,并通过诱导凋亡抑制这些滑膜细胞的增殖。这些研究结果提示,PLK-1在导致骨质破坏的RA滑膜细胞增殖中起关键作用,针对PLK-1的siRNA可能对RA治疗有用。