Pneumocystis cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells
Pneumocystis cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells
复制标题
DOI：
10.1186/1465-9921-11-95
复制
发表时间：
2010-07-13
影响因子：
5.8
通讯作者：
Limper, Andrew H.
中科院分区：
文献类型：
--
作者：
Carmona, Eva M.;Lamont, Jeffrey D.;Limper, Andrew H.
背景资料：肺孢子虫肺炎期间继发于肺泡炎症的呼吸衰竭是免疫功能低下患者死亡的主要原因。肺孢子虫感染患者肺内的神经浸润可预测感染的严重程度和死亡。先前的几项研究表明，气道上皮细胞通过NF-κ B依赖性途径释放中性粒细胞趋化蛋白MIP-2（啮齿动物）和IL-8（人类），以响应肺孢子虫和纯化的肺孢子虫细胞壁β-葡聚糖（PCBG）。然而，对于PCBG激活气道上皮细胞导致IL-8分泌的分子机制知之甚少。方法：为了解决这个问题，我们研究了不同的钙依赖性丝裂原活化蛋白激酶（MAPK）在人气道上皮细胞系1HAEo-细胞中的激活。我们的数据提供的证据表明，PCBG诱导MAPK，ERK和p38的磷酸化，NF-κ B的激活和随后的IL-8的分泌以钙依赖性的方式。此外，我们评估了鞘糖脂作为β-葡聚糖在人气道上皮细胞中可能的受体的作用。预孵育的细胞与D-苏型-1-苯基-2-癸酰氨基-3-吗啉代-1-丙醇（PGEF）的鞘糖脂合成的一个有效的抑制剂，之前PCBG的刺激，显着降低IL-8 production.Conclusion：这些数据表明，PCBG激活钙依赖性MAPK信号导致释放IL-8的过程中，需要鞘糖脂的最佳信号。
Background: Respiratory failure secondary to alveolar inflammation during Pneumocystis pneumonia is a major cause of death in immunocompromised patients. Neutrophil infiltration in the lung of patients with Pneumocystis infection predicts severity of the infection and death. Several previous studies indicate that airway epithelial cells release the neutrophil chemoattractant proteins, MIP-2 (rodents) and IL-8 (humans), in response to Pneumocystis and purified Pneumocystis cell wall beta-glucans (PCBG) through the NF-kappa B-dependent pathway. However, little is known about the molecular mechanisms that are involved in the activation of airway epithelium cells by PCBG resulting in the secretion of IL-8.Method: To address this, we have studied the activation of different calcium-dependent mitogen-activated protein kinases (MAPKs) in 1HAEo-cells, a human airway epithelial cell line.Results: Our data provide evidence that PCBG induces phosphorylation of the MAPKs, ERK, and p38, the activation of NF-kappa B and the subsequently secretion of IL-8 in a calcium-dependent manner. Further, we evaluated the role of glycosphingolipids as possible receptors for beta-glucans in human airway epithelial cells. Preincubation of the cells with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) a potent inhibitor of the glycosphingolipids synthesis, prior to PCBG stimulation, significantly decreased IL-8 production.Conclusion: These data indicate that PCBG activates calcium dependent MAPK signaling resulting in the release of IL-8 in a process that requires glycosphingolipid for optimal signaling.