Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells

Lemjabbar, Hassan; Basbaum, Carol

doi:10.1038/nm0102-41

Cited by 333 publications

(301 citation statements)

References 25 publications

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“…Hypothesized that the TLR2-MyD88-NF-κB pathway plays a crucial role in PGNinduced MUC5AC expression (Thai et al, 2008). Interestingly, S. pyogenes PGN could not induce MUC2 gene expression, whereas lipoteichoic acid (LTA) was able to do so in HM3 cells (Lemjabbar et al, 2002). The discrepancy of PGN signaling in S. aureus versus S. pyogenes may derive from the difference in pathogeneses of these two bacteria in the airway.…”

Section: Discussionmentioning

confidence: 99%

Peptidoglycan from Staphylococcus aureus Increases MUC5AC Gene Expression via RSK1-CREB Pathway in Human Airway Epithelial Cells

Kim

Jung

Choi

et al. 2011

Molecules and Cells

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Respiratory tract exposure to viruses, air pollutants, or bacterial pathogens can lead to pulmonary diseases. The molecular mechanism of mucous overproduction increased by these pathogens provides the knowledge for developing new therapeutic strategies. There is established in vitro data demonstrating that the overexpression of MUC5AC is induced by peptidoglycan (PGN) derived from Staphylococcus aureus. However, the mechanisms by which PGN activates MUC5AC gene expression in the airway remain unclear. The aim of this study was to identify the mechanism of PGN-induced MUC5AC gene expression. We found that PGN could induce MUC5AC gene expressions in a time-and dose-dependent manner. Moreover, activations of ERK1/2 and JNK increased after treatment of cells with PGN, whereas phosporylation of p38 was undetected. Of these MAPKs, pharmacologic inhibition of ERK1/2 decreased PGN-induced MUC5AC gene expression. In addition, we checked the activation of p90 ribosomal S6 kinase 1 (RSK1) as a downstream signaling target of ERK1/2 in PGN signaling. The activation of RSK1 was prevented by pretreatment with PD98059. We also found that RSK1 mediated the PGN-induced phosphorylation of cAMP response element-binding protein (CREB) and the transcription of MUC5AC. Furthermore, the cAMPresponse element (CRE) in the MUC5AC promoter appears to be important for PGN-induced MUC5AC gene expression in NCI-H292 cells.

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Section: Discussionmentioning

confidence: 99%

Peptidoglycan from Staphylococcus aureus Increases MUC5AC Gene Expression via RSK1-CREB Pathway in Human Airway Epithelial Cells

Kim

Jung

Choi

et al. 2011

Molecules and Cells

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“…NF-κB activation in airway epithelial cells is a common event during inflammatory conditions. Utilizing bacterial extracts from P. aeruginosa and Staphylococcus aureus, investigators found that that LPS and LTA can induce MUC2 expression in the colon epithelial cell line HM3 (32,33). Further studies showed that both signaled through the activation of Ras-MEK1/2-ERK1/2 pathways.…”

Section: Muc2 Expression Regulated By Mitogen-activated Protein Kinasmentioning

confidence: 99%

“…LTA does not act directly on Ras but instead first activates ADAM10, a matrix metalloprotease (MMP), to cleave membrane-bound pro-EGF (epidermal growth factor) to release free EGF ligands. These EGF ligands then bind to EGFR, which then activates RAS-MEK1/2-ERK1/2, as does LPS, to cause NF-κB activation of MUC2 transcription (33). P. aeruginosa also has a protein called flagellin that can activate airway epithelial cells and MUC2 expression (34).…”

Section: Muc2 Expression Regulated By Mitogen-activated Protein Kinasmentioning

confidence: 99%

Regulation of Airway Mucin Gene Expression

Thai

Loukoianov

Wachi

et al. 2008

Annu. Rev. Physiol.

193

223

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Mucins are important components that exert a variety of functions in cell-cell interaction, epidermal growth factor receptor signaling, and airways protection. In the conducting airways of the lungs, mucins are the major contributor to the viscoelastic property of mucous secretion, which is the major barrier to trapping inhaled microbial organism, particulates, and oxidative pollutants. The homeostasis of mucin production is an important feature in conducting airways for the maintenance of mucociliary function. Aberrant mucin secretion and accumulation in airway lumen are clinical hallmarks associated with various lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and lung cancer. Among 20 known mucin genes identified, 11 of them have been verified at either the mRNA and/or protein level in airways. The regulation of mucin genes is complicated, as are the mediators and signaling pathways. This review summarizes the current view on the mediators, the signaling pathways, and the transcriptional units that are involved in the regulation of airway mucin gene expression. In addition, we also point out essential features of epigenetic mechanisms for the regulation of these genes.

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“…Mucin concentration in broncoalveolar lavage is increased in response to LPS and flagella, and MUC5A gene expression is upregulated by LPS and Gram-positive and Gram-negative bacteria 78 as well as pro-inflammatory chemokines and cytokines expressed by airway epithelial cells. 79 MUC2 expression is also increased in response to P. aeruginosa LPS and flagellin, 80,81 S. aureus lipoteichoic acid 82 and H. influenzae 83 by signaling cascades that share common elements with those induced by TLRs.…”

Section: Airway Epithelial Cell Responses To Bacteriamentioning

confidence: 99%

Airway epithelial cell signaling in response to bacterial pathogens

Gómez

Prince

2007

Pediatric Pulmonology

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Summary. The airway epithelium represents a primary site for the introduction and deposition of potentially pathogenic microorganisms into the body, through inspired air. The epithelial mucosa is an important component of the innate immune system that recognizes conserved structures in microorganisms and initiates appropriate signaling to recruit and activate phagocytic cells to the airways. This review focuses on how airway epithelial cells sense and respond to the presence of bacterial pathogens. The major signaling cascades initiated by epithelial receptors that lead to phagocyte recruitment to the airways as well as the ability of the epithelium to regulate inflammation are discussed.

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Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells

Cited by 333 publications

References 25 publications

Peptidoglycan from Staphylococcus aureus Increases MUC5AC Gene Expression via RSK1-CREB Pathway in Human Airway Epithelial Cells

Peptidoglycan from Staphylococcus aureus Increases MUC5AC Gene Expression via RSK1-CREB Pathway in Human Airway Epithelial Cells

Regulation of Airway Mucin Gene Expression

Airway epithelial cell signaling in response to bacterial pathogens

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