The role of Toll-like receptors 2 and 4 on reactive oxygen species and nitric oxide production by macrophage cells stimulated with root canal pathogens

The role of Toll-like receptors 2 and 4 on reactive oxygen species and nitric oxide production by macrophage cells stimulated with root canal pathogens
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DOI:
10.1111/j.1399-302x.2008.00432.x
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发表时间:
2008-10-01
影响因子:
--
通讯作者:
Sobrinho, A. P. R.
Sobrinho, A. P. R.
中科院分区:
其他
文献类型:
--
作者:
Marcato, L. G.;Ferlini, A. P.;Sobrinho, A. P. R.

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前言:根尖周病变是由于宿主对根管感染的免疫反应的激活和相互作用而产生的。最近鉴定的Toll样受体(TLR)似乎参与识别和发展针对无数微生物的免疫应答。然而,很少的信息是可用的TLR在根尖周lesions.Method诱导的作用:TLR-2和TLR-4在激活小鼠巨噬细胞的作用进行了研究,用具核梭杆菌和厌氧消化链霉菌刺激。结果:TLR-2和TLR-4参与了活化巨噬细胞产生活性氧(ROS)的过程。无论是否添加干扰素-γ(IFN-γ),微生物诱导TLR-2活性和TLR-2缺陷的巨噬细胞产生相似水平的NO,排除了TLR-2在这些细菌诱导的NO产生中的作用。在不添加IFN-γ的情况下,只有厌氧假单胞菌诱导TLR-4感受态巨噬细胞产生NO。而IFN-γ添加后,F.核仁诱导巨噬细胞产生NO。结论:TLR-2可能参与诱导巨噬细胞产生ROS,而只有F.核质诱导TLR-4感受态巨噬细胞产生活性氧。这两种微生物显着诱导大量的NO独立的TLR-2和TLR-4。我们的结论是,微生物可能参与根尖周病变的诱导和进展,通过NO和活性氧的生产激活的巨噬细胞。
Introduction: Periapical lesions arise as a result of the activation and interaction of the host immune responses against root canal infection. Recently identified Toll-like receptors (TLR) seem to be involved in the recognition and development of immune responses against a myriad of microorganisms. However, very little information is available on the role of TLR in the induction of periapical lesions.Method: The role of TLR-2 and TLR-4 in the activation of murine macrophages stimulated using Fusobacterium nucleatum and Peptostreptococcus anaerobius was investigated. The production of nitric oxide (NO) and reactive oxygen species (ROS) was assessed.Results: The results demonstrate that TLR-2 and TLR-4 are involved in the production of ROS by activated macrophages. The microorganisms induced similar levels of NO production by TLR-2-competent and TLR-2-deficient macrophages, regardless of the addition of interferon-gamma (IFN-gamma), ruling out a role for TLR-2 in the NO production induced by these bacteria. Only P. anaerobius induced NO production by TLR-4-competent macrophages without the addition of IFN-gamma. However, after IFN-gamma addition, F. nucleatum induced macrophage NO production. Therefore, NO production stimulated by IFN-gamma and these microorganisms seems to be TLR-4-independent.Conclusion: TLR-2 seems to be involved in the induction of ROS production by macrophages in response to prevalent root canal bacteria, while only F. nucleatum induced ROS production by TLR-4-competent macrophages. Both microorganisms significantly induced large amounts of NO independent of TLR-2 and TLR-4. We conclude that microorganisms may participate in the induction and progression of periapical lesions through NO and ROS production by activated macrophages.