Dataset Information

Glucocorticoids Elevate Pseudomonas aeruginosa Binding to Airway Epithelium by Upregulating Syndecan-1 Expression.

ABSTRACT: Glucocorticoids are commonly used for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids are associated with a significantly increased risk of pneumonia. Syndecan-1 (SDC1) located in the cell membrane of airway epithelial cell is the crucial molecule mediating infections by P. aeruginosa (PA). In the present study, we found that SDC1 expression was upregulated and the adhesion of PA to human bronchial epithelial (HBE) cells increased to 125 and 138%, respectively, after stimulation by dexamethasone or budesonide. The HBE cells knocking down SDC1 showed lower affinity to PA compared with control. CCAAT-enhancer-binding protein β (C/EBP β) and its phosphorylated form participated in the regulation of glucocorticoid to SDC1 for interfering C/EBP β or inhibiting phosphorylation of C/EBP β by LiCl and BIO, which are inhibitors of glycogen synthase kinase 3β (GSK-3β), and could prevent glucocorticoids from upregulating SDC1 expression. One should be cautious in administering glucocorticoids in chronic lung disease because of their property of increasing the expression of SDC1 and PA binding to the airway epithelium.

SUBMITTER: Liu D

PROVIDER: S-EPMC8591732 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Glucocorticoids Elevate <i>Pseudomonas aeruginosa</i> Binding to Airway Epithelium by Upregulating Syndecan-1 Expression.

Liu Dong D Zeng Ying-Ying YY Shi Meng-Meng MM Qu Jie-Ming JM

Frontiers in microbiology 20211101

Glucocorticoids are commonly used for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids are associated with a significantly increased risk of pneumonia. Syndecan-1 (SDC1) located in the cell membrane of airway epithelial cell is the crucial molecule mediating infections by <i>P. aeruginosa</i> (PA). In the present study, we found that SDC1 expression was upregulated and the adhesion of PA to human bronchial epithelial (HBE) cells increased to 125 a ...[more]

PMID: 34790176

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Project description:Pseudomonas aeruginosa, an important opportunistic pathogen of man, exploits numerous factors for initial attachment to the host, an event required to establish bacterial infection. In this paper, we rigorously explore the role of two major bacterial adhesins, type IV pili (Tfp) and flagella, in bacterial adherence to distinct host receptors at the apical (AP) and basolateral (BL) surfaces of polarized lung epithelial cells and induction of subsequent host signaling and pathogenic events. Using an isogenic mutant of P. aeruginosa that lacks flagella or utilizing beads coated with purified Tfp, we establish that Tfp are necessary and sufficient for maximal binding to host N-glycans at the AP surface of polarized epithelium. In contrast, experiments utilizing a P. aeruginosa isogenic mutant that lacks Tfp or using beads coated with purified flagella demonstrate that flagella are necessary and sufficient for maximal binding to heparan sulfate (HS) chains of heparan sulfate proteoglycans (HSPGs) at the BL surface of polarized epithelium. Using two different cell-free systems, we demonstrate that Tfp-coated beads show highest binding affinity to complex N-glycan chains coated onto plastic plates and preferentially aggregate with beads coated with N-glycans, but not with single sugars or HS. In contrast, flagella-coated beads bind to or aggregate preferentially with HS or HSPGs, but demonstrate little binding to N-glycans. We further show that Tfp-mediated binding to host N-glycans results in activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway and bacterial entry at the AP surface. At the BL surface, flagella-mediated binding to HS activates the epidermal growth factor receptor (EGFR), adaptor protein Shc, and PI3K/Akt, and induces bacterial entry. Remarkably, flagella-coated beads alone can activate EGFR and Shc. Together, this work provides new insights into the intricate interactions between P. aeruginosa and lung epithelium that may be potentially useful in the development of novel treatments for P. aeruginosa infections.

Project description:BackgroundThe respiratory tract epithelium is a critical environmental interface that regulates inflammation. In chronic infectious airway diseases, pathogens may permanently colonize normally sterile luminal environments. Host-pathogen interactions determine the intensity of inflammation and thus, rates of tissue injury. Although many cells become refractory to stimulation by pathogen products, it is unknown whether the airway epithelium becomes either tolerant or hypersensitive in the setting of chronic infection. Our goals were to characterize the response of well-differentiated primary human tracheobronchial epithelial cells to Pseudomonas aeruginosa, to understand whether repeated exposure induced tolerance and, if so, to explore the mechanism(s).MethodsThe apical surface of well-differentiated primary human tracheobronchial epithelial cell cultures was repetitively challenged with Pseudomonas aeruginosa culture filtrates or the bacterial media control. Toxicity, cytokine production, signal transduction events and specific effects of dominant negative forms of signaling molecules were examined. Additional experiments included using IL-1beta and TNFalpha as challenge agents, and performing comparative studies with a novel airway epithelial cell line.ResultsAn initial challenge of the apical surface of polarized human airway epithelial cells with Pseudomonas aeruginosa culture filtrates induced phosphorylation of IRAK1, JNK, p38, and ERK, caused degradation of IkappaBalpha, generation of NF-kappaB and AP-1 transcription factor activity, and resulted in IL-8 secretion, consistent with activation of the Toll-like receptor signal transduction pathway. These responses were strongly attenuated following a second Pseudomonas aeruginosa, or IL-1beta, but not TNFalpha, challenge. Tolerance was associated with decreased IRAK1 protein content and kinase activity and dominant negative IRAK1 inhibited Pseudomonas aeruginosa--stimulated NF-kappaB transcriptional activity.ConclusionThe airway epithelial cell response to Pseudomonas aeruginosa entails adaptation and tolerance likely mediated, in part, by down-regulation of IRAK1.

Dataset Information

Glucocorticoids Elevate Pseudomonas aeruginosa Binding to Airway Epithelium by Upregulating Syndecan-1 Expression.

Publications

Glucocorticoids Elevate <i>Pseudomonas aeruginosa</i> Binding to Airway Epithelium by Upregulating Syndecan-1 Expression.

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