Elevated CD14 (Cluster of Differentiation 14) and Toll-Like Receptor (TLR) 4 Signaling Deteriorate Periapical Inflammation in TLR2 Deficient Mice.
Elevated CD14 (Cluster of Differentiation 14) and Toll-Like Receptor (TLR) 4 Signaling Deteriorate Periapical Inflammation in TLR2 Deficient Mice.
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DOI：
10.1002/ar.23383
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Sasaki H
中科院分区：
文献类型：
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作者：
Rider D;Furusho H;Xu S;Trachtenberg AJ;Kuo WP;Hirai K;Susa M;Bahammam L;Stashenko P;Fujimura A;Sasaki H
根尖牙周炎（根尖周病变）是一种由感染引起的颌骨慢性炎症，最终导致根尖牙周组织的破坏。Toll样受体（TLR）在病原体的初始识别中是突出的。我们以前的研究表明，TLR 4信号是在根尖周病变引起的多微生物牙髓感染的促炎。相反，TLR 2在根尖周组织破坏的调节中的功能作用仍然没有完全理解。使用TLR 2缺陷（KO）、TLR 2/TLR 4双缺陷（dKO）和野生型（WT）小鼠，我们证明TLR 2 KO小鼠对多种微生物感染诱导的根尖周病变高度反应，所述根尖周病变由TLR 4信号转导通路过度激活引起，导致NF-κB（核因子κ B）和促炎细胞因子产生升高。改变的TLR 4信号传导是由CD 14（分化簇14）的TLR 2缺陷依赖性升高引起的，CD 14是TLR 4的共受体。事实上，CD 14的中和在体外和体内显著抑制TLR 2缺陷依赖性炎症和组织破坏。我们的研究结果表明，TLR 2，TLR 4和CD 14的网络是调节多微生物牙槽感染和随后的组织破坏的关键因素。
Apical periodontitis (periapical lesions) is an infection-induced chronic inflammation in the jaw, ultimately resulting in the destruction of apical periodontal tissue. Toll-like receptors (TLRs) are prominent in the initial recognition of pathogens. Our previous study showed that TLR4 signaling is proinflammatory in periapical lesions induced by a polymicrobial endodontic infection. In contrast, the functional role of TLR2 in regulation of periapical tissue destruction is still not fully understood. Using TLR2 deficient (KO), TLR2/TLR4 double deficient (dKO), and wild-type (WT) mice, we demonstrate that TLR2 KO mice are highly responsive to polymicrobial infection-induced periapical lesion caused by over activation of TLR4 signal transduction pathway that resulted in elevation of NF-κB (nuclear factor kappa B) and proinflammatory cytokine production. The altered TLR4 signaling is caused by TLR2 deficiency-dependent elevation of CD14 (cluster of differentiation 14), which is a co-receptor of TLR4. Indeed, neutralization of CD14 strikingly suppresses TLR2 deficiency-dependent inflammation and tissue destruction in vitro and in vivo. Our findings suggest that a network of TLR2, TLR4, and CD14 is a key factor in regulation of polymicrobial dentoalveolar infection and subsequent tissue destruction.