CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest.
CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest.
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CCR5 信号传导促进脂多糖诱导的巨噬细胞募集和肺泡发育停滞
DOI：
10.1038/s41419-021-03464-7
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发表时间：
2021-02-15
影响因子：
9
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Chen Z;Xie X;Jiang N;Li J;Shen L;Zhang Y
支气管肺发育不良（BPD）的发病机制涉及炎症，其机制尚未完全表征。在这里，我们报告C-C趋化因子受体5（CCR 5）及其配体的过度表达与BPD的发展。脂多糖诱导的BPD大鼠CCR 5和白细胞介素-1 β（IL-1β）水平增加，肺泡化减少，而CCR 5或IL-1β受体拮抗剂治疗减少炎症并增加肺泡化。CCR 5增强巨噬细胞迁移、肺中的巨噬细胞浸润、IL-1β水平、赖氨酰氧化酶活性和肺泡发育停滞。BPD婴儿血液样品中单核细胞上的CCR 5表达及其配体升高。此外，补充鲨肝醇降低了暴露于脂多糖的大鼠肺中CCR 5的表达和IL-1β的产生。此外，CCR 5培养的RIP 3 −/−巨噬细胞的受体相互作用激酶3（RIP 3）上游调节因子表现出部分阻断脂多糖诱导的CCR 5表达。我们的结论是CCR 5表达增加是BPD发展的关键机制，代表了一种新的治疗靶点。
The pathogenesis of bronchopulmonary dysplasia (BPD), involves inflammatory, mechanisms that are not fully characterized. Here we report that overexpression of C-C chemokine receptor 5 (CCR5) and its ligands is associated with BPD development. Lipopolysaccharide-induced BPD rats have increased CCR5 and interleukin-1β (IL-1β) levels, and decreased alveolarization, while CCR5 or IL-1β receptor antagonist treatments decreased inflammation and increased alveolarization. CCR5 enhances macrophage migration, macrophage infiltration in the lungs, IL-1β levels, lysyl oxidase activity, and alveolar development arrest. CCR5 expression on monocytes, and its ligands in blood samples from BPD infants, are elevated. Furthermore, batyl alcohol supplementation reduced CCR5 expression and IL-1β production in lipopolysaccharide-exposed rat lungs. Moreover, receptor-interacting kinase 3 (RIP3) upstream regulator of CCR5-cultured RIP3−/−macrophages exhibited partly blocked lipopolysaccharide-induced CCR5 expression. We conclude that increased CCR5 expression is a key mechanism in BPD development and represents a novel therapeutic target for treatment.
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影响因子：
29
作者：
Baker RG;Hayden MS;Ghosh S
通讯作者：
Ghosh S
影响因子：
46.9
作者：
Chua, Robert Lorenz;Lukassen, Soeren;Eils, Roland
通讯作者：
Eils, Roland
DOI：
10.1152/ajplung.90405.2008
发表时间：
2009-05-01
影响因子：
4.9
作者：
Cao, Lei;Wang, Jinxia;Post, Martin
通讯作者：
Post, Martin
影响因子：
16.6
作者：
Liao J;Kapadia VS;Brown LS;Cheong N;Longoria C;Mija D;Ramgopal M;Mirpuri J;McCurnin DC;Savani RC
通讯作者：
Savani RC
影响因子：
20.3
作者：
Kuipers, Hedwich F.;Biesta, Paula J.;van den Elsen, Peter J.
通讯作者：
van den Elsen, Peter J.