Interactions between NF-κB and SP3 Connect Inflammatory Signaling with Reduced FGF-10 Expression

Carver, Billy J.; Plosa, Erin J.; Stinnett, Amanda; Blackwell, Timothy S.; Prince, Lawrence S.

doi:10.1074/jbc.m112.447318

Cited by 33 publications

(35 citation statements)

References 54 publications

(39 reference statements)

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“…NF- κ B involvement in TNF- α -induced ANP down-regulation is not opposed to the proinflammatory role of this transcription factor, being ANP a molecule that exerts an anti-inflammatory effect in airway epithelial cells [48]. Regarding the mechanism linking NF- κ B to the downregulation of ANP gene expression, we suggest that it could be similar to that recently proposed for Fibroblast Growth Factor 10 (FGF-10), where NF- κ B activation may lead to reduced gene expression, by recruiting inhibitory factors to specific gene promoters [51]. …”

Section: Discussionmentioning

confidence: 81%

TNF-αRegulates Natriuretic Peptides and Aquaporins in Human Bronchial Epithelial Cells BEAS-2B

Mezzasoma

Cagini

Antognelli

et al. 2013

Mediators of Inflammation

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Postoperative-fluid retention is a severe complication frequently reported in patients undergoing major surgical procedures. The complex network of molecules involved in such a severe surgery-induced condition remains poorly understood. Inflammation has been proposed among the various causes of fluid retention. Since TNF-α is one of the main proinflammatory cytokine initially released after major surgery, it is reasonable to assume its involvement in fluid overload. Here, we showed that TNF-α selectively regulates key molecules involved in fluids balance, such as natriuretic peptides (NPs) and aquaporins, in human bronchial epithelial cells BEAS-2B. In particular, we found that TNF-α induced a decrease of arial natriuretic peptide, natriuretic peptide receptor-1, aquaporin-1 and aquaporin-5 and an increase of brain natriuretic peptide with a different involvement of nuclear factor-κB and mitogen-activated protein kinases signaling pathway activation. Moreover, the observed changes in NPs expression, demonstrate inflammation as an additional cause of brain natriuretic peptide elevation, adding an important piece of information in the novel area of study regarding NPs and inflammation. Finally, we suggest that inflammation is one of the mechanisms of Aquaporin-1 and aquaporin-5 expression regulation. Therefore, in this exploratory study, we speculate that TNF-α might be involved in postoperative-fluid retention related to major surgery.

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Section: Discussionmentioning

confidence: 81%

TNF-αRegulates Natriuretic Peptides and Aquaporins in Human Bronchial Epithelial Cells BEAS-2B

Mezzasoma

Cagini

Antognelli

et al. 2013

Mediators of Inflammation

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“…Although the role of macrophages during alveolarization is not well understood, we and others have shown that macrophages and macrophage-derived products disrupt branching morphogenesis (Blackwell et al, 2011;Nold et al, 2013). Specifically, we have found that products of activated macrophages can impair expression of molecules by epithelial and mesenchymal cells that are important for control of airway branching, including BMP4, Wnt7b and FGF10 (Benjamin et al, 2010;Blackwell et al, 2011;Carver et al, 2013). We speculate that mediators secreted by activated macrophages might also disrupt crucial epithelialmesenchymal interactions required for normal septation and remodeling of the interstitium.…”

Section: Discussionmentioning

confidence: 95%

Epithelial β1 integrin is required for lung branching morphogenesis and alveolarization

et al. 2014

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Integrin-dependent interactions between cells and extracellular matrix regulate lung development; however, specific roles for β1-containing integrins in individual cell types, including epithelial cells, remain incompletely understood. In this study, the functional importance of β1 integrin in lung epithelium during mouse lung development was investigated by deleting the integrin from E10.5 onwards using surfactant protein C promoter-driven Cre. These mutant mice appeared normal at birth but failed to gain weight appropriately and died by 4 months of age with severe hypoxemia. Defects in airway branching morphogenesis in association with impaired epithelial cell adhesion and migration, as well as alveolarization defects and persistent macrophagemediated inflammation were identified. Using an inducible system to delete β1 integrin after completion of airway branching, we showed that alveolarization defects, characterized by disrupted secondary septation, abnormal alveolar epithelial cell differentiation, excessive collagen I and elastin deposition, and hypercellularity of the mesenchyme occurred independently of airway branching defects. By depleting macrophages using liposomal clodronate, we found that alveolarization defects were secondary to persistent alveolar inflammation. β1 integrin-deficient alveolar epithelial cells produced excessive monocyte chemoattractant protein 1 and reactive oxygen species, suggesting a direct role for β1 integrin in regulating alveolar homeostasis. Taken together, these studies define distinct functions of epithelial β1 integrin during both early and late lung development that affect airway branching morphogenesis, epithelial cell differentiation, alveolar septation and regulation of alveolar homeostasis.

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“…Recent studies show that NF-kB can indirectly regulate SP1-dependent gene expression by modifying SP1/DNA binding (33,34). These studies showed that NF-kB interferes with SP1 binding through an analogous transcription factor (SP3).…”

Section: Discussionmentioning

confidence: 99%

Thrombin Down-Regulates Tissue Factor Pathway Inhibitor Expression in a PI3K/Nuclear Factor-κB–Dependent Manner in Human Pleural Mesothelial Cells

Jeffers¹,

Owens²,

Koenig³

et al. 2015

Am J Respir Cell Mol Biol

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Tissue factor pathway inhibitor (TFPI) is the primary inhibitor of the extrinsic coagulation cascade, and its expression is reported to be relatively stable. Various pathophysiologic agents have been shown to influence TFPI activity by regulating its expression or by modifying the protein. It is not clear how TFPI activity is regulated in normal physiology or in injury. Because thrombin and TFPI are locally elaborated in pleural injury, we sought to determine if thrombin could regulate TFPI in human pleural mesothelial cells (HPMCs). Thrombin significantly decreased TFPI mRNA and protein levels by . 70%. Thrombin-mediated down-regulation of TFPI promoted factor X activation by HPMCs. The ability of thrombin to significantly decrease TFPI mRNA and protein levels was maintained at nanomolar concentrations. Protease-activated receptor (PAR)-1, a mediator of thrombin signaling, is detectable in the mesothelium in human and murine pleural injury. PAR-1 silencing blocked thrombin-mediated decrements of TFPI in HPMCs. Thrombin activates PI3K/Akt and nuclear factor kB (NF-kB) signaling in HPMCs. Inhibition of PI3K (by PX-866) and NF-kB (by SN50) prevented thrombin-mediated TFPI mRNA and protein downregulation. These are the first studies to demonstrate that thrombin decreases TFPI expression in HPMCs. Our findings demonstrate a novel mechanism by which thrombin regulates TFPI expression in HPMCs and promotes an unrestricted procoagulant response, and suggest that interactions between PI3K and NF-kB signaling pathways are linked in HPMCs and control TFPI expression. These findings raise the possibility that targeting this pathway could limit the ability of the mesothelium to support extravascular fibrin deposition and organization associated with pleural injury.

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Interactions between NF-κB and SP3 Connect Inflammatory Signaling with Reduced FGF-10 Expression

Cited by 33 publications

References 54 publications

TNF-αRegulates Natriuretic Peptides and Aquaporins in Human Bronchial Epithelial Cells BEAS-2B

TNF-αRegulates Natriuretic Peptides and Aquaporins in Human Bronchial Epithelial Cells BEAS-2B

Epithelial β1 integrin is required for lung branching morphogenesis and alveolarization

Thrombin Down-Regulates Tissue Factor Pathway Inhibitor Expression in a PI3K/Nuclear Factor-κB–Dependent Manner in Human Pleural Mesothelial Cells

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