Surfactant protein (SP)-A suppresses preterm delivery and inflammation via TLR2.
Surfactant protein (SP)-A suppresses preterm delivery and inflammation via TLR2.
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DOI：
10.1371/journal.pone.0063990
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hirsch E
中科院分区：
文献类型：
--
作者：
Agrawal V;Smart K;Jilling T;Hirsch E
Toll样受体（TLR）是启动对病原体的先天免疫应答的模式识别分子。肺表面活性蛋白（SP）-A是内源性产生的TLR 2和TLR 4的配体。SP-A已被提议作为小鼠分娩开始的胎儿产生的信号。我们研究了SP-A与致病性TLR激动剂脂多糖（LPS）、肽聚糖（PGN）和聚肌苷酸：胞苷酸（poly（I：C））（分别为TLR 4、TLR 2和TLR 3的配体）之间的相互作用对炎症介质表达和早产的影响。将三种类型的小鼠巨噬细胞（细胞系RAW 264.7，和新鲜羊水和腹膜巨噬细胞，包括来自TLR 4和TLR 2敲除小鼠的巨噬细胞）用致病性TLR激动剂与或不与SP-A一起处理长达7小时。SP-A单独对小鼠巨噬细胞中的炎性介质没有影响，并且不能独立地诱导早产。SP-A通过TLR 2依赖性机制显著抑制TLR配体诱导的炎症介质（白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α和趋化因子CCL 5）的表达。在小鼠炎症诱导的早产模型中，子宫内施用SP-A显著抑制早产，抑制促炎介质的表达，并增强CXCL 1和抗炎介质IL-10的表达。我们的结论是SP-A通过TLR 2抑制TLR配体诱导的早产和炎症反应。
Toll like receptors (TLRs) are pattern-recognition molecules that initiate the innate immune response to pathogens. Pulmonary surfactant protein (SP)-A is an endogenously produced ligand for TLR2 and TLR4. SP-A has been proposed as a fetally produced signal for the onset of parturition in the mouse. We examined the effect of interactions between SP-A and the pathogenic TLR agonists lipopolysaccharide (LPS), peptidoglycan (PGN) and polyinosinic:cytidylic acid (poly(I:C)) (ligands for TLR4, TLR2 and TLR3, respectively) on the expression of inflammatory mediators and preterm delivery. Three types of mouse macrophages (the cell line RAW 264.7, and fresh amniotic fluid and peritoneal macrophages, including macrophages from TLR4 and TLR2 knockout mice) were treated for up to 7 hours with pathogenic TLR agonists with or without SP-A. SP-A alone had no effect upon inflammatory mediators in mouse macrophages and did not independently induce preterm labor. SP-A significantly suppressed TLR ligand-induced expression of inflammatory mediators (interleukin (IL)-1β, tumor necrosis factor (TNF)-α and the chemokine CCL5) via a TLR2 dependent mechanism. In a mouse inflammation-induced preterm delivery model, intrauterine administration of SP-A significantly inhibited preterm delivery, suppressed the expression of proinflammatory mediators and enhanced the expression of the CXCL1 and anti-inflammatory mediator IL-10. We conclude that SP-A acts via TLR2 to suppress TLR ligand-induced preterm delivery and inflammatory responses.
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影响因子：
4.4
作者：
Henning, Lisa N.;Azad, Abul K.;Schlesinger, Larry S.
通讯作者：
Schlesinger, Larry S.
DOI：
10.1152/ajplung.1994.267.6.l712
发表时间：
1994-12-01
影响因子：
4.9
作者：
KREMLEV, SG;PHELPS, DS
通讯作者：
PHELPS, DS
影响因子：
2.2
作者：
Kankavi, Orhan;Ata, Ayhan;Gungor, Orsan
通讯作者：
Gungor, Orsan
影响因子：
2.9
作者：
Leong, Anthony S. -Y;Norman, Jane E.;Smith, Roger
通讯作者：
Smith, Roger
关于表面活性剂蛋白A在人肺中的重要性。
影响因子：
2.6
作者：
Goldmann T;Kähler D;Schultz H;Abdullah M;Lang DS;Stellmacher F;Vollmer E
通讯作者：
Vollmer E