Local complement-targeted intervention in periodontitis: proof-of-concept using a C5a receptor (CD88) antagonist.
Local complement-targeted intervention in periodontitis: proof-of-concept using a C5a receptor (CD88) antagonist.
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DOI：
10.4049/jimmunol.1202339
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发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
Hajishengallis G
中科院分区：
文献类型：
--
作者：
Abe T;Hosur KB;Hajishengallis E;Reis ES;Ricklin D;Lambris JD;Hajishengallis G
当补体过度激活或失调时，补体成为感染和炎症病理学（包括牙周炎）之间的主要联系。这种口腔炎性疾病与微生物群失调有关，导致骨骼和其他牙齿支撑结构的破坏，并对全身健康产生不利影响。我们以前已经表明，小鼠缺乏补体C5 a受体（C5 aR; CD 88）或TLR 2是高度和相似的牙周炎的抵抗力，这表明这两种受体之间的串扰可能参与疾病的过程。在这里，我们表明，C5 aR和TLR 2确实协同最大的炎症反应在牙周组织和发现一个新的药理学目标，以消除牙周炎。使用两种不同的小鼠牙周炎模型，我们表明，局部治疗与C5 aR拮抗剂抑制牙周炎症通过下调TNF，IL-1β，IL-6和IL-17，并进一步防止骨丢失，无论TLR 2的存在。这些发现不仅揭示了C5 aR和TLR 2在牙周炎症中的重要合作，而且为局部靶向C5 aR作为治疗人类牙周炎的有力候选者提供了概念验证。
When excessively activated or deregulated, complement becomes a major link between infection and inflammatory pathology including periodontitis. This oral inflammatory disease is associated with a dysbiotic microbiota, leads to the destruction of bone and other tooth-supporting structures, and exerts an adverse impact on systemic health. We have previously shown that mice deficient either in complement C5a receptor (C5aR; CD88) or TLR2 are highly and similarly resistant to periodontitis, suggesting that a crosstalk between the two receptors may be involved in the disease process. Here we show that C5aR and TLR2 indeed synergize for maximal inflammatory responses in the periodontal tissue and uncover a novel pharmacological target to abrogate periodontitis. Using two different mouse models of periodontitis, we show that local treatments with a C5aR antagonist inhibited periodontal inflammation through downregulation of TNF, IL-1β, IL-6, and IL-17 and further protected against bone loss, regardless of the presence of TLR2. These findings not only reveal a crucial co-operation between C5aR and TLR2 in periodontal inflammation, but provide proof-of-concept for local targeting of C5aR as a powerful candidate for the treatment of human periodontitis.
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Keystone-Pathogen假设。
DOI：
10.1038/nrmicro2873
发表时间：
2012-10
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
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影响因子：
30.5
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影响因子：
3.5
作者：
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通讯作者：
Opstad, P. K.
影响因子：
3.7
作者：
Hajishengallis G;Lamont RJ
通讯作者：
Lamont RJ
影响因子：
4.4
作者：
Burns, Elia;Bachrach, Gilad;Nussbaum, Gabriel
通讯作者：
Nussbaum, Gabriel