Stimulation of α7 nicotinic acetylcholine receptor inhibits CD14 and the toll-like receptor 4 expression in human monocytes
Stimulation of α7 nicotinic acetylcholine receptor inhibits CD14 and the toll-like receptor 4 expression in human monocytes
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DOI：
10.1097/01.shk.0000228168.86845.60
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发表时间：
2006-10-01
期刊：
影响因子：
3.1
通讯作者：
Tanaka, Noriaki
中科院分区：
文献类型：
--
作者：
Hamano, Ryosuke;Takahashi, Hideo Kohka;Tanaka, Noriaki
脂多糖（LPS）-受体复合物，CD 14/Toll样受体4，已知在脓毒症期间的免疫应答中发挥作用。据报道，过度炎症和肿瘤坏死因子（TNF）-α合成可导致内毒素血症和脓毒症的发病率和死亡率。通过单核细胞上的细胞间粘附分子1、B7.1和CD 40与T细胞上的其配体之间的接合的细胞间相互作用已被认为在炎症反应如TNF-α和白细胞介素10的产生中起作用。尼古丁通过刺激烟碱乙酰胆碱受体α 7亚单位（α 7-nAChR）而具有抗炎作用，现已成为人们关注的焦点。然而，关于尼古丁对LPS诱导的免疫应答的抑制作用的机制知之甚少。在本研究中，我们发现，尼古丁抑制CD 14，Toll样受体4，细胞间粘附分子1，B7.1，和CD 40的表达单核细胞和TNF-α的产生，但不是白细胞介素10，在人外周血单核细胞在LPS的存在下。尼古丁的作用分别被非选择性和选择性α 7-nAChR拮抗剂美加明和α-银环蛇毒素逆转。因此，尼古丁可能通过α 7-nAChR抑制LPS受体复合物的表达，从而导致粘附分子表达和TNF-α产生的减少。此外，我们证明了核因子-κ B和p38丝裂原活化蛋白激酶抑制剂在LPS存在下模拟尼古丁的作用。提示核因子-κ B和p38丝裂原活化蛋白激酶可能参与了尼古丁的作用。
The lipopolysaccharide (LPS)-receptor complex, CD14/toll-like receptor 4, is known to play a role in the immune responses during sepsis. Excessive inflammation and tumor necrosis factor (TNF)-alpha synthesis have been reported to cause morbidity and mortality in endotoxemia and sepsis. Cell-to-cell interaction through the engagement between intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and their ligands on T cells has been suggested to play a role in the inflammatory response such as TNF-alpha and interleukin 10 production. Nicotine, with the stimulation of the nicotinic acetylcholine receptor alpha 7 subunit (alpha 7-nAChR), has now become the focus of attention because of its anti-inflammatory effects. However, little is known about the mechanism of the inhibitory effects induced by nicotine on the LPS-induced immune responses. In the present study, we found that nicotine suppressed the expression of CD14, toll-like receptor 4, intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and the production of TNF-alpha, but not interleukin 10, in human peripheral blood mononuclear cells in the presence of LPS. The actions of nicotine were reversed by a nonselective and a selective alpha 7-nAChR antagonist, mecamylamine and a-bungarotoxin, respectively. Therefore, nicotine might inhibit the LPS receptor complex expression via alpha 7-nAChR, thus leading to a decrease in the adhesion molecule expression and TNF-alpha production. Moreover, we demonstrated that a nuclear factor-kappa B and a p38 mitogen-activated protein kinase inhibitor mimicked the actions of nicotine in the presence of LPS. These results suggested that the nuclear factor-kappa B and p38 mitogen-activated protein kinase might be involved in the actions of nicotine.