Effects of low-dose doxycycline on cytokine secretion in human monocytes stimulated with Aggregatibacter actinomycetemcomitans

Effects of low-dose doxycycline on cytokine secretion in human monocytes stimulated with Aggregatibacter actinomycetemcomitans
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DOI:
10.1016/j.cyto.2011.08.039
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发表时间:
2011-12-01
期刊:
影响因子:
3.8
通讯作者:
McKay, I. J.
McKay, I. J.
中科院分区:
医学3区
文献类型:
--
作者:
Bostanci, N.;Akguel, B.;McKay, I. J.

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强力霉素是一种抗生素,用于治疗各种炎症性疾病,包括牙周炎。除了其抗菌特性外,这种药物在亚抗菌剂量下也具有独立的抗炎作用。本研究旨在探讨低剂量多西环素(LDD)对牙周致病菌伴放线菌聚集杆菌(Aggregatibacteractinomycetemcomitans)攻击的人单核细胞产生细胞因子的影响。用人细胞因子芯片检测12种细胞因子的同时调节。为了验证阵列结果,还通过酶联免疫吸附测定(ELISA)测量了选定的细胞因子。A.伴放线菌刺激细胞产生肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1 α、IL-1 β、IL-6和IL-8,而强力霉素显著抑制这种作用。这种调节的动力学证明了促炎细胞因子的早期(2小时内)和显著(P < 0.05)抑制,抗炎细胞因子IL-10的轻度(0.5倍)上调。结果表明,LDD在A.伴放线菌该模型提供了明确的证据,证明LDD的一些临床证明的益处可能与其调节单核细胞释放炎症介质的能力有关。这种特性可能有助于临床证明这种抗生素作为牙周炎的预防性治疗的益处。(C)2011爱思唯尔有限公司保留所有权利。
Doxycycline is an antibiotic used in the treatment of a variety of inflammatory conditions, including periodontitis. Apart from its antimicrobial properties, this drug also has independent anti-inflammatory effects at sub-antimicrobial doses. The present study aimed to investigate the effects of low-doses of doxycycline (LDD) on cytokine production by human monocytic cells challenged with the periodontal pathogen Aggregatibacter actinomycetemcomitans, for up to 6 h. The simultaneous regulation of 12 cytokines were measured by a Human Cytokine Array Kit. To validate the array findings, selected cytokines were also measured by enzyme-linked immunosorbant assay (ELISA). A. actinomycetemcomitans stimulated the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-6 and IL-8 by the cells after 6 h of challenge, and doxycycline significantly inhibited this effect. The kinetics of this regulation demonstrated an early (within 2 h) and significant (P < 0.05) inhibition of pro-inflammatory cytokines, with a mild (0.5-fold) up-regulation of the anti-inflammatory cytokine IL-10. The results indicate that LDD acts as an anti-inflammatory agent in human monocytic cells stimulated with A. actinomycetemcomitans. This model provides clear evidence that some of the clinically proven benefits of LDD may be related to its ability to regulate inflammatory mediator release by monocytic cells. This property may contribute to the clinically proven benefits of this antibiotic as an adjunctive treatment for periodontitis. (C) 2011 Elsevier Ltd. All rights reserved.