Endo Wataru, Arito Mitsumi, Sato Toshiyuki, Kurokawa Manae S, Omoteyama Kazuki, Iizuka Nobuko, Okamoto Kazuki, Suematsu Naoya, Nakamura Hiroshi, Beppu Moroe, Kato Tomohiro
Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine , Kanagawa , Japan.
Mod Rheumatol. 2014 Sep;24(5):844-50. doi: 10.3109/14397595.2013.864225. Epub 2013 Dec 11.
Sulfasalazine (SSZ) and tofacitinib are effective for treating rheumatoid arthritis, however, their effects on chondrocytes have not been fully understood. We here tried to elucidate their effects on chondrocyte proteins.
We treated chondrocytes from five osteoarthritis patients with IL-1β, IL-1β+ SSZ, IL-1β+ tofacitinib, SSZ alone, and tofacitinib alone. Then, we compared protein profiles of the chondrocytes using two-dimensional differential gel electrophoresis. Further, we identified altered proteins by mass spectrometry.
Out of 892 detected protein spots, the IL-1β stimulation changed intensity of 43 spots more than 1.3-fold or less than 1/1.3-fold significantly. SSZ suppressed the IL-1β-induced intensity alteration in 16 (37%) out of the 43 protein spots. Tofacitinib suppressed the IL-1β-induced alteration in 4 (9.3%) out of the 43 spots. The production of AMP deaminase 2 and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 were increased by IL-1β and the increase was suppressed by SSZ and by tofacitinib. SSZ alone altered intensity of 273 (31%) out of the 852 spots significantly, whereas tofacitinib alone altered intensity of only 24 (2.7%) out of them.
SSZ and, to lesser extent, tofacitinib suppress the effects of IL-1β on the protein profiles of chondrocytes. Our data would promote understanding of effects of the drugs on chondrocytes.
柳氮磺胺吡啶（SSZ）和托法替布对类风湿性关节炎有效，然而，它们对软骨细胞的作用尚未完全明确。我们在此试图阐明它们对软骨细胞蛋白质的影响。
我们用白细胞介素-1β（IL-1β）、IL-1β + SSZ、IL-1β + 托法替布、单独的SSZ以及单独的托法替布处理来自5名骨关节炎患者的软骨细胞。然后，我们使用二维差异凝胶电泳比较软骨细胞的蛋白质谱。此外，我们通过质谱鉴定变化的蛋白质。
在检测到的892个蛋白质斑点中，IL-1β刺激使43个斑点的强度显著变化超过1.3倍或低于1/1.3倍。SSZ抑制了43个蛋白质斑点中16个（37%）由IL-1β诱导的强度变化。托法替布抑制了43个斑点中4个（9.3%）由IL-1β诱导的变化。IL-1β增加了AMP脱氨酶2和原胶原赖氨酸2-氧代戊二酸5-双加氧酶2的产生，而SSZ和托法替布抑制了这种增加。单独使用SSZ使852个斑点中的273个（31%）强度显著改变，而单独使用托法替布仅使其中24个（2.7%）强度改变。
SSZ以及程度较轻的托法替布抑制IL-1β对软骨细胞蛋白质谱的影响。我们的数据将促进对这些药物对软骨细胞作用的理解。
