Blockage of P2X7 attenuates acute lung injury in mice by inhibiting NLRP3 inflammasome.
Blockage of P2X7 attenuates acute lung injury in mice by inhibiting NLRP3 inflammasome.
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阻断P2X7通过抑制NLRP3炎性小体减轻小鼠急性肺损伤。
DOI：
10.1016/j.intimp.2015.04.035
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发表时间：
2015-07
影响因子：
5.6
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Wang S;Zhao J;Wang H;Liang Y;Yang N;Huang Y
NLRP 3炎性体参与急性肺损伤（ALI）过程中的炎症反应。据报道，嘌呤能受体P2 X7位于NLRP 3激活的上游。然而，P2 X7在ALI中的治疗意义仍有待探索。本研究采用脂多糖（LPS）诱导的小鼠模型来研究P2 X7阻断在ALI中的治疗潜力。我们的研究结果表明，P2 X7/NLRP 3炎性体途径在ALI小鼠的肺中与对照小鼠相比显著上调。P2 X7拮抗剂A438079可抑制NLRP 3/ASC/caspase 1的活化、IL-1β、IL-17 A和IFN-γ的产生以及中性粒细胞浸润，但不抑制IL-10的产生，从而显著改善肺损伤。此外，阻断P2 X7显著抑制骨髓源性巨噬细胞中的NLRP 3炎性体活化和IL-1β产生。在体内使用另一种P2 X7抑制剂亮蓝G（BBG）获得了类似的结果。因此，药物阻断P2 X7/NLRP 3通路可以被认为是ALI患者的潜在治疗策略。P2 X7/NLRP 3通路在急性肺损伤（ALI）小鼠中被激活。阻断P2 X7可抑制ALI小鼠中NLRP 3炎性小体的活化。阻断P2 X7抑制细胞因子产生和中性粒细胞浸润。药物阻断P2 X7对ALI具有治疗潜力。
NLRP3 inflammasome is engaged in the inflammatory response during acute lung injury (ALI). Purinergic receptor P2X7 has been reported to be upstream of NLRP3 activation. However, the therapeutic implication of P2X7 in ALI remains to be explored. The present study used lipopolysaccharide (LPS)-induced mouse model to investigate the therapeutic potential of P2X7 blockage in ALI. Our results showed that P2X7/NLRP3 inflammasome pathway was significantly upregulated in the lungs of ALI mice as compared with control mice. P2X7 antagonist A438079 suppressed NLRP3/ASC/caspase 1 activation, production of IL-1β, IL-17A and IFN-γ and neutrophil infiltration but not the production of IL-10, resulting in a significant amelioration of lung injury. Moreover, blockage of P2X7 significantly inhibited NLRP3 inflammasome activation and IL-1β production in bone marrow derived macrophages. Similar results were obtained using another P2X7 inhibitor brilliant blue G (BBG) in vivo. Thus, pharmacological blockage of P2X7/NLRP3 pathway can be considered as a potential therapeutic strategy in patients with ALI. P2X7/NLRP3 pathway is activated in mice with acute lung injury (ALI). Blockade of P2X7 suppressed NLRP3 inflammasome activation in mice with ALI. Blockade of P2X7 suppressed cytokine production and neutrophil infiltration. Pharmacological blockage of P2X7 has therapeutic potential on ALI.
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DOI：
10.4049/jimmunol.0903937
发表时间：
2010-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
He X;Mekasha S;Mavrogiorgos N;Fitzgerald KA;Lien E;Ingalls RR
通讯作者：
Ingalls RR
DOI：
10.1016/j.bbrc.2004.05.048
发表时间：
2004-07-02
影响因子：
3.1
作者：
Chen, ZM;Jin, NL;Liu, L
通讯作者：
Liu, L
影响因子：
2
作者：
Kong, H.;Wang, Y.;Dai, S.
通讯作者：
Dai, S.
影响因子：
4.4
作者：
Perregaux, DG;McNiff, P;Gabel, CA
通讯作者：
Gabel, CA
影响因子：
5.3
作者：
Ray, FR;Huang, W;Barden, JA
通讯作者：
Barden, JA