Blocking proinflammatory cytokine release modulates peripheral blood mononuclear cell response to Porphyromonas gingivalis.
Blocking proinflammatory cytokine release modulates peripheral blood mononuclear cell response to Porphyromonas gingivalis.
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DOI：
10.1902/jop.2012.120422
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发表时间：
2013-09
影响因子：
4.3
通讯作者：
Van Dyke TE
中科院分区：
文献类型：
--
作者：
Berker E;Kantarci A;Hasturk H;Van Dyke TE
慢性牙周炎是一种炎症性疾病，细胞因子在疾病的进展中起主要作用。据报道，在患病的牙周组织中，抗炎细胞因子(IL-4和IL-10)缺失或减少，这表明促炎和抗炎介质之间存在失衡。我们已经验证了这样的假设，即存在由促炎和抗炎细胞因子介导的细胞串扰，并且阻断促炎细胞因子(肿瘤坏死因子-α和IL-1)的产生将增强外周血单核细胞(PBMC)对牙龈假单胞菌的抗炎细胞因子(IL-4和IL-10)的产生。从诊断为慢性牙周炎的患者或健康人分离PBMC，培养24小时。刀豆蛋白A(ConA)作为淋巴细胞功能的激活剂。用活的和热灭活的牙龈假单胞菌或牙龈假单胞菌的脂多糖作为细菌刺激剂。抗肿瘤坏死因子α和白介素1α或α或β的抗体可中和肿瘤坏死因子α和IL 1α或β的产生。用酶联免疫吸附试验检测培养上清液中肿瘤坏死因子α、白介素1β、白介素4和白介素10的产生。活的牙龈假单胞菌不会导致任何显著的IL-10或IL-4的释放，而与来自健康人和牙周炎患者的未经刺激或活的牙龈假单胞菌刺激的细胞相比，热致死的牙龈假单胞菌导致IL-10水平显著增加。总体而言，慢性牙周炎患者的PBMC对ConA和牙龈假单胞菌的反应产生的IL-10显著降低，这表明抗炎细胞因子的产生受到慢性抑制。阻断促炎细胞因子反应不会导致IL-10或IL-4对活体牙龈假单胞菌的反应发生任何实质性变化。阻断促炎细胞因子反应恢复了慢性牙周炎细胞对牙周炎杆菌脂多糖的反应产生IL-10。这些发现表明，慢性牙周炎患者的PBMC已经抑制了抗炎细胞因子的产生，这种细胞因子的产生可以通过中和促炎细胞因子来部分恢复。单核细胞是产生IL-10的重要来源，单核细胞来源的IL-10可能在慢性牙周炎的发病机制中起调节作用。
Chronic periodontitis is an inflammatory disease in which cytokines play a major role in the progression of disease. Anti-inflammatory cytokines (IL-4 and IL-10) were reported to be absent or reduced in diseased periodontal tissues, suggesting an imbalance between the pro- and anti-inflammatory mediators. We have tested the hypothesis that there is cellular cross-talk mediated by pro- and anti-inflammatory cytokines and that blocking pro-inflammatory cytokine (TNF-α and IL-1) production will enhance anti-inflammatory cytokine (IL-4 and IL-10) production from peripheral blood mononuclear cells (PBMC) in response to P. gingivalis. PBMC were isolated from individuals diagnosed with chronic periodontitis or healthy individuals and cultured for 24 hours. Concanavalin-A (ConA) was used as an activator of lymphocyte function. Live and heat-killed P .gingivalis or lipopolysaccharide from P. gingivalis was used as the bacterial stimulants. TNF-α and IL-1 production was neutralized by specific antibodies against TNF-α and IL-1α or β. Culture supernatants were evaluated by ELISA for TNF-α, IL-1β, IL-4, and IL-10 production. Live P. gingivalis did not result in any significant IL-10 or IL-4 release while heat-killed P. gingivalis led to a significant increase in IL-10 levels compared to unstimulated or live P. gingivalis-stimulated cells from both healthy and periodontitis individuals. Overall, PBMC from patients with chronic periodontitis produced significantly lower IL-10 in response to ConA and P. gingivalis suggesting chronic suppression of the anti-inflammatory cytokine production. Blocking the pro-inflammatory cytokine response did not result in any substantial change in IL-10 or IL-4 response to live P. gingivalis. Blocking the pro-inflammatory cytokine response restored IL-10 production by cells from chronic periodontitis in response to P. gingivalis LPS. These findings suggest that PBMC from patients with chronic periodontitis have suppressed anti-inflammatory cytokine production that can, in part, be restored by neutralizing pro-inflammatory cytokines. Monocytes are an important source of IL-10 production and monocyte-derived IL-10 might play a regulatory role in the pathogenesis of chronic periodontitis.
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DOI：
10.1902/annals.1998.3.1.108
发表时间：
1998-07-01
期刊：
Annals of periodontology
影响因子：
--
作者：
Page, R C
通讯作者：
Page, R C
影响因子：
3.8
作者：
Hamedi, M.;Belibasakis, G. N.;Bostanci, N.
通讯作者：
Bostanci, N.
影响因子：
3.5
作者：
Pradeep, A. R.;Roopa, Y.;Swati, P. P.
通讯作者：
Swati, P. P.
影响因子：
4.3
作者：
Bozkurt, FY;Berker, E;Bulut, S
通讯作者：
Bulut, S
影响因子：
4.3
作者：
Bartold, PM;Marshall, RI;Haynes, DR
通讯作者：
Haynes, DR