Melatonin inhibits Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-6 in murine macrophages by suppressing NF-κB and STAT1 activity
Melatonin inhibits Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-6 in murine macrophages by suppressing NF-κB and STAT1 activity
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DOI：
10.1111/j.1600-079x.2010.00829.x
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发表时间：
2011-03-01
影响因子：
10.3
通讯作者：
Kim, Sung-Jo
中科院分区：
文献类型：
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作者：
Choi, Eun-Young;Jin, Ji-Young;Kim, Sung-Jo
虽然褪黑激素的一系列生物学和药理学活性已被报道，但对其在牙周病中的潜在抗炎功效知之甚少。在这项研究中，我们研究了褪黑激素对小鼠巨噬细胞产生炎症介质的影响，由中间普雷沃氏菌（Prevotella intermedia）的脂多糖（LPS）刺激，牙周炎性反应的主要原因，并试图确定潜在的作用机制。褪黑激素在基因转录和翻译水平上抑制中间对虾LPS激活的RAW 264.7细胞中一氧化氮（NO）和白细胞介素-6（IL-6）的产生。褪黑素能显著抑制中间偃麦草LPS诱导的NF-κ B依赖的荧光素酶活性。褪黑激素在I κ B-α降解水平上不降低NF-κ B转录活性。褪黑素通过抑制NF-κ B B p50亚基的核转位和DNA结合活性阻断NF-κ B B信号通路，并抑制STAT 1信号通路。虽然需要进一步的研究，以澄清详细的作用机制，我们的结论是，褪黑激素可能有助于阻断主机的破坏性过程介导的这两个促炎介质，并可能是一个非常有效的调制器的主机响应炎症性牙周病的治疗。
Although a range of biological and pharmacological activities of melatonin have been reported, little is known about its potential anti-inflammatory efficacy in periodontal disease. In this study, we investigated the effects of melatonin on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory reactions in the periodontium, and sought to determine the underlying mechanisms of action. Melatonin suppressed the production of nitric oxide (NO) and interleukin-6 (IL-6) at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. P. intermedia LPS-induced NF-kappa B-dependent luciferase activity was significantly inhibited by melatonin. Melatonin did not reduce NF-kappa B transcriptional activity at the level of I kappa B-alpha degradation. Melatonin blocked NF-kappa B signaling through the inhibition of nuclear translocation and DNA-binding activity of NF-kappa B p50 subunit and suppressed STAT1 signaling. Although further research is required to clarify the detailed mechanism of action, we conclude that melatonin may contribute to blockade of the host-destructive processes mediated by these two proinflammatory mediators and could be a highly efficient modulator of host response in the treatment of inflammatory periodontal disease.