Muramyldipeptide modulates CXCL-8 release of BEAS-2B cells via NOD2
Muramyldipeptide modulates CXCL-8 release of BEAS-2B cells via NOD2
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DOI：
10.1111/j.1365-3083.2008.02145.x
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发表时间：
2008-09-01
影响因子：
3.7
通讯作者：
Schulz, C.
中科院分区：
文献类型：
--
作者：
Farkas, L.;Stoelcker, B.;Schulz, C.
慢性炎症和急性加重是慢性阻塞性肺疾病（COPD）的病理生理特征。对细菌病原体的免疫反应受损可能导致这两种情况。核苷酸寡聚化结构域2（nucleotide oligomerization domain 2，NOD 2）是胞壁酰二肽（muramyldipeptide，MDP）的细胞内天然免疫受体。NOD 2基因突变导致MDP识别能力下降与同种异体干细胞移植和脓毒症患者的慢性肠道炎症和肺部并发症相关。我们的研究提供了证据表明，NOD 2，Toll样受体4（TLR 4）和衔接蛋白受体相互作用蛋白2（RIP 2）诱导肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）在支气管上皮细胞系BEAS-2B。我们还表明，脂多糖（LPS）可以进一步增加NOD 2转录在TNF-α和IFN-γ诱导的激活状态。此外，我们表明，虽然MDP未能增强CXCL-8释放，否则未受刺激的BEAS-213细胞12 - 11，预刺激期与TNF-α和IFN-γ引发的细胞通过诱导NOD 2和RIP 2的CXCL-8分泌的额外增加。LPS本身显著增加CXCL-8的产生，并且MDP的共施用进一步增加细胞因子分泌。最后，与NOD 2野生型过表达相比，SNP 13突变体的过表达降低了BEAS-213细胞中MDP诱导的趋化因子的产生。综上所述，我们的工作表明，MDP和NOD 2通过MDP和LPS之间的协同相互作用对LPS攻击后BEAS-213细胞的CXCL-8释放起重要作用。
Chronic inflammation and acute exacerbations are pathophysiological features of chronic obstructive pulmonary disease (COPD). An impaired immune response to bacterial pathogens can contribute to both of them. Nucleotide oligomerization domain 2 (NOD2) is an intracellular receptor of innate immunity for muramyldipeptide (MDP). Mutations of the NOD2 gene followed by decreased recognition of MDP are associated with chronic intestinal inflammation and pulmonary complications of patients with allogenic stem cell transplant and sepsis. Our study provides evidence that NOD2, toll-like receptor 4 (TLR4) and the adapter protein receptor-interacting protein 2 (RIP2) are induced by tumor-necrosis factor-alpha (TNF-alpha,) and interferon-gamma (IFN-gamma) in the bronchial epithelial cell line BEAS-2B. We also demonstrate that lipopolysaccharide (LPS) can further increase NOD2 transcription in a TNF-alpha and IFN-gamma-induced activation state. In addition, we show that, while MDP fails to I enhance CXCL-8 release from otherwise unstimulated BEAS-213 cells a 12 11, prestimulation period with TNF-alpha and IFN-gamma primes the cells for an additional increase of CXCL-8 secretion via induction of NOD2 and RIP2. LPS itself significantly augments CXCL-8 production and co-administration of MDP further increases cytokine secretion. Finally, overexpression of an SNP 13 mutant decreased MDP-induced chemokine production in BEAS-213 cells compared with NOD2 wild type overexpression. Taken together, our work indicates that MDP and NOD2 play an important role for CXCL-8 release of BEAS-213 cells following LPS-challenge via synergistic interactions between MDP and LPS.