<it>Pneumocystis </it>cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells

<p>Abstract</p> <p>Background</p> <p>Respiratory failure secondary to alveolar inflammation during <it>Pneumocystis </it>pneumonia is a major cause of death in immunocompromised patients. Neutrophil infiltration in the lung of patients with <it>Pneumoc...

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Main Authors: Limper Andrew H, Wylam Mark, Xue Ailing, Lamont Jeffrey D, Carmona Eva M
Format: Article
Language:English
Published: BMC 2010-07-01
Series:Respiratory Research
Online Access:http://respiratory-research.com/content/11/1/95
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author Limper Andrew H
Wylam Mark
Xue Ailing
Lamont Jeffrey D
Carmona Eva M
author_facet Limper Andrew H
Wylam Mark
Xue Ailing
Lamont Jeffrey D
Carmona Eva M
author_sort Limper Andrew H
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Respiratory failure secondary to alveolar inflammation during <it>Pneumocystis </it>pneumonia is a major cause of death in immunocompromised patients. Neutrophil infiltration in the lung of patients with <it>Pneumocystis </it>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 <it>Pneumocystis </it>and purified <it>Pneumocystis </it>cell wall β-glucans (PCBG) through the NF-κB-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.</p> <p>Method</p> <p>To address this, we have studied the activation of different calcium-dependent mitogen-activated protein kinases (MAPKs) in 1HAEo<sup>- </sup>cells, a human airway epithelial cell line.</p> <p>Results</p> <p>Our data provide evidence that PCBG induces phosphorylation of the MAPKs, ERK, and p38, the activation of NF-κB and the subsequently secretion of IL-8 in a calcium-dependent manner. Further, we evaluated the role of glycosphingolipids as possible receptors for β-glucans in human airway epithelial cells. Preincubation of the cells with D-<it>threo</it>-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.</p> <p>Conclusion</p> <p>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.</p>
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spelling doaj.art-956894d2a89b493eb851d7b349a566792022-12-22T02:41:10ZengBMCRespiratory Research1465-99212010-07-011119510.1186/1465-9921-11-95<it>Pneumocystis </it>cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cellsLimper Andrew HWylam MarkXue AilingLamont Jeffrey DCarmona Eva M<p>Abstract</p> <p>Background</p> <p>Respiratory failure secondary to alveolar inflammation during <it>Pneumocystis </it>pneumonia is a major cause of death in immunocompromised patients. Neutrophil infiltration in the lung of patients with <it>Pneumocystis </it>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 <it>Pneumocystis </it>and purified <it>Pneumocystis </it>cell wall β-glucans (PCBG) through the NF-κB-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.</p> <p>Method</p> <p>To address this, we have studied the activation of different calcium-dependent mitogen-activated protein kinases (MAPKs) in 1HAEo<sup>- </sup>cells, a human airway epithelial cell line.</p> <p>Results</p> <p>Our data provide evidence that PCBG induces phosphorylation of the MAPKs, ERK, and p38, the activation of NF-κB and the subsequently secretion of IL-8 in a calcium-dependent manner. Further, we evaluated the role of glycosphingolipids as possible receptors for β-glucans in human airway epithelial cells. Preincubation of the cells with D-<it>threo</it>-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.</p> <p>Conclusion</p> <p>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.</p>http://respiratory-research.com/content/11/1/95
spellingShingle Limper Andrew H
Wylam Mark
Xue Ailing
Lamont Jeffrey D
Carmona Eva M
<it>Pneumocystis </it>cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells
Respiratory Research
title <it>Pneumocystis </it>cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells
title_full <it>Pneumocystis </it>cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells
title_fullStr <it>Pneumocystis </it>cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells
title_full_unstemmed <it>Pneumocystis </it>cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells
title_short <it>Pneumocystis </it>cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells
title_sort it pneumocystis it cell wall β glucan stimulates calcium dependent signaling of il 8 secretion by human airway epithelial cells
url http://respiratory-research.com/content/11/1/95
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