KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells
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KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells Zhongbing Liu,1 Dongmei Zhang,1,2 Chi Sun,1 Ran Tao,1 Xinbao Xu,1 Libin Xu,1 Hongbing Cheng,3 Min Xiao,4 and Youhua Wang1,5
Abstract—Karyopherin-α2 (KPNA2) functions as an adaptor that transports several proteins to the nucleus. We investigated the function and possible mechanisms of KPNA2 involved in rheumatoid arthritis (RA). Western blotting and immunohistochemistry showed the protein expression of KPNA2 increased in synovial tissue of RA patients compared with the healthy controls. Double immunofluorescent staining indicated that KPNA2 co-localized with T cells, macrophage-like synoviocytes, fibroblast-like synoviocytes, and neutrophils in synovial tissue of RA patients. Moreover, the expression of KPNA2 in SW982 cells was increased in a time-dependent manner in response to TNFα stimulation. Both Western blotting and immunofluorescent staining assay revealed the co-localization of KPNA2 and P65 and their translocation from cytoplasma in TNFα-treated SW982 cells. Furthermore, knocking down the expression of KPNA2 by siRNA inhibited TNFα-induced expression of IL-6, MMP-1, and MMP-13 and, more importantly, decreased the P65 phosphorylation in SW982 cells. We therefore suggested that KPNA2 may play a key role in the inflammation process of RA via NF-κB P65 signal transduction pathway. KEY WORDS: karyopherin-α2 (KPNA2); rheumatoid arthritis (RA); SW982; tumor necrosis factor-α (TNFα); P65.
INTRODUCTION Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease which is characterized by infiltration of inflammatory cell and resulting in synovial hyperplasia and joint destruction [1, 2]. The pathogenesis of proliferation has still not been clarified, but the characteristics of Zhongbing Liu and Dongmei Zhang contributed equally to this work. 1
Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001Jiangsu Province, China 2 Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, China 3 Department of Orthopaedics, Traditional Chinese Medical Hospital of Nantong City, Nantong, 226001, China 4 National Glycoengineering Research Center and State Key Laboratory of Microbial Technology, Shandong University, Jinan, 250100, China 5 To whom correspondence should be addressed at Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001Jiangsu Province, China. E-mail: [email protected]
RA synoviocytes are similar to those of transformed cells [3]. NF-κB, one of the major transcription factor implicated in joint inflammation, is essential for the production of cytokines and proteases by RA fibroblast-like synoviocytes (FLSs), and it mediates the resistance of RA FLS to apoptosis [4–6]. In humans, the synov
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