Mor-Vaknin Nirit, Punturieri Antonello, Sitwala Kajal, Faulkner Neil, Legendre Maureen, Khodadoust Michael S, Kappes Ferdinand, Ruth Jeffrey H, Koch Alisa, Glass David, Petruzzelli Lilli, Adams Barbara S, Markovitz David M
Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical Center, Ann Arbor, MI 48109-0640, USA.
Mol Cell Biol. 2006 Dec;26(24):9484-96. doi: 10.1128/MCB.01030-06. Epub 2006 Oct 9.
The nuclear DNA-binding protein DEK is an autoantigen that has been implicated in the regulation of transcription, chromatin architecture, and mRNA processing. We demonstrate here that DEK is actively secreted by macrophages and is also found in synovial fluid samples from patients with juvenile arthritis. Secretion of DEK is modulated by casein kinase 2, stimulated by interleukin-8, and inhibited by dexamethasone and cyclosporine A, consistent with a role as a proinflammatory molecule. DEK is secreted in both a free form and in exosomes, vesicular structures in which transcription-modulating factors such as DEK have not previously been found. Furthermore, DEK functions as a chemotactic factor, attracting neutrophils, CD8+ T lymphocytes, and natural killer cells. Therefore, the DEK autoantigen, previously described as a strictly nuclear protein, is secreted and can act as an extracellular chemoattractant, suggesting a direct role for DEK in inflammation.
核DNA结合蛋白DEK是一种自身抗原,与转录调控、染色质结构和mRNA加工有关。我们在此证明,DEK由巨噬细胞主动分泌,并且在青少年关节炎患者的滑液样本中也能发现。DEK的分泌受酪蛋白激酶2调节,受白细胞介素-8刺激,并被地塞米松和环孢素A抑制,这与它作为促炎分子的作用一致。DEK以游离形式和外泌体形式分泌,外泌体是一种囊泡结构,此前尚未在其中发现诸如DEK等转录调节因子。此外,DEK作为趋化因子发挥作用,吸引中性粒细胞、CD8+T淋巴细胞和自然杀伤细胞。因此,先前被描述为严格意义上的核蛋白的DEK自身抗原会被分泌出来,并可作为细胞外趋化剂,这表明DEK在炎症中具有直接作用。