691: Vitamin D reduces TNF-α induced MMP-9 activity in human fetal airway smooth muscle cells

2014 ◽  
Vol 210 (1) ◽  
pp. S340
Author(s):  
Arij Faksh ◽  
Rodney Britt ◽  
Elizabeth Vogel ◽  
Elizabeth Baldwin ◽  
Mari Charisse Trinidad ◽  
...  
Keyword(s):  
Vitamin D ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Tnf Α

Raf-1 kinase mediates adenylyl cyclase sensitization by TNF-α in human airway smooth muscle cells

2007 ◽  
Vol 292 (6) ◽  
pp. L1414-L1421 ◽  
Author(s):  
Yoko Osawa ◽  
Peter D. Yim ◽  
Dingbang Xu ◽  
Reynold A. Panettieri ◽  
Charles W. Emala
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Airway Smooth Muscle ◽  
Egf Receptor ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Tnf Α

Tumor necrosis factor (TNF)-α is a potent inflammatory cytokine implicated in the exacerbation of asthma. Chronic exposure to TNF-α has been reported to induce G protein-coupled receptor desensitization, but adenylyl cyclase sensitization, in airway smooth muscle cells by an unknown mechanism. Cyclic AMP, which is synthesized by adenylyl cyclases in response to G protein-coupled receptor signals, is an important second messenger involved in the regulation of the airway muscle proliferation, migration, and tone. In other cell types, TNF-α receptors transactivate the EGF receptor, which activates raf-1 kinase. Further studies in transfected cells show that raf-1 kinase can phosphorylate and activate some isoforms of adenylyl cyclase. Cultured human airway smooth muscle cells were treated with TNF-α in the presence or absence of inhibitors of prostaglandin signaling, protein kinases, or Gi proteins. TNF-α caused a significant dose- (1–10 ng/ml) and time-dependent (24 and 48 h) increase in forskolin-stimulated adenylyl cyclase activity, which was abrogated by pretreatment with GW5074 (a raf-1 kinase inhibitor), was partially inhibited by an EGF receptor inhibitor, but was unaffected by pertussis toxin. TNF-α also increased phosphorylation of Ser338 on raf-1 kinase, indicative of activation. IL-1β and EGF sensitization of adenylyl cyclase activity was also sensitive to raf-1 kinase inhibition by GW5074. Taken together, these studies link two signaling pathways not previously characterized in human airway smooth muscle cells: TNF-α transactivation of the EGF receptor, with subsequent raf-1 kinase-mediated activation of adenylyl cyclase.

Selected Contribution: Synergism between TNF-α and IL-1β in airway smooth muscle cells: implications for β-adrenergic responsiveness

2001 ◽  
Vol 91 (3) ◽  
pp. 1467-1474 ◽  
Author(s):  
Paul E. Moore ◽  
Thomas Lahiri ◽  
Johanne D. Laporte ◽  
Trudi Church ◽  
Reynold A. Panettieri ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Nuclear Factor Κb ◽  
Airway Smooth Muscle Cells ◽  
Nuclear Factor ◽  
Tnf Α ◽  
Combined Administration ◽  
Cox 2

In human cultured airway smooth muscle cells, interleukin (IL)-1β increases cyclooxygenase (COX)-2 expression and PGE2 release, ultimately resulting in decreased β-adrenergic responsiveness. In this study, we aimed to determine whether tumor necrosis factor-α (TNF-α) synergizes with IL-1β in the induction of these events. TNF-α alone, at concentrations up to 10 ng/ml, had no effect on COX-2 protein expression; at concentrations as low as 0.1 ng/ml, it significantly enhanced the ability of IL-1β (0.2 ng/ml) to induce COX-2 and to increase PGE2 release. IL-1β and TNF-α in combination also significantly enhanced COX-2 promoter activity, indicating that synergism between the cytokines is mediated at the level of gene transcription. Although IL-1β and TNF-α each increased nuclear factor-κB activation and induced extracellular regulated kinase and p38 phosphorylation, combined administration of the cytokines did not enhance either nuclear factor-κB or mitogen-activated protein kinase activation. Combined administration of IL-1β (0.2 ng/ml) and TNF-α (0.1 or 1.0 ng/ml) reduced the ability of isoproterenol to decrease human airway smooth muscle cell stiffness, as measured by magnetic twisting cytometry, even though individually these cytokines, at these concentrations, had no effect on isoproterenol responses. Treatment with the selective COX-2 inhibitor NS-398 abolished the synergistic effects of TNF-α and IL-1β on β-adrenergic responsiveness. Our results indicate that low concentrations of IL-1β and TNF-α synergize to promote β-adrenergic hyporesponsiveness and that effects on COX-2 expression and PGE2 are responsible for these events. The data suggest that the simultaneous release in the airway, of even very small amounts of cytokines, can have important functional consequences.

scholarly journals Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-α and dexamethasone

2008 ◽  
Vol 9 (1) ◽  
Author(s):  
Krishnaswamy G Tirumurugaan ◽  
Bit Na Kang ◽  
Reynold A Panettieri ◽  
Douglas N Foster ◽  
Timothy F Walseth ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Tnf Α

scholarly journals Vitamin D Attenuates Cytokine-Induced Remodeling in Human Fetal Airway Smooth Muscle Cells

2015 ◽  
Vol 230 (6) ◽  
pp. 1189-1198 ◽  
Author(s):  
Rodney D. Britt ◽  
Arij Faksh ◽  
Elizabeth R. Vogel ◽  
Michael A. Thompson ◽  
Vivian Chu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells

TNF-α upregulates Giα and Gqα protein expression and function in human airway smooth muscle cells

1999 ◽  
Vol 276 (3) ◽  
pp. L405-L411 ◽  
Author(s):  
Kunihisa Hotta ◽  
Charles W. Emala ◽  
Carol A. Hirshman
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Signal Transduction Pathways ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Tnf Α ◽  
And Function

Chronic inflammation is a characteristic feature of asthma. Multiple inflammatory mediators are released within the asthmatic lung, some of which may have detrimental effects on signal transduction pathways in airway smooth muscle. The effects of tumor necrosis factor (TNF)-α on the expression and function of muscarinic receptors and guanine nucleotide-binding protein (G protein) α-subunits were examined in human airway smooth muscle cells. Cultured human airway smooth muscle cells were incubated in serum-free culture medium for 72 h in the presence and absence of 10 ng/ml of TNF-α, after which the cells were lysed and subjected to electrophoresis and Gαi-2, Gqα, and Gsα protein subunits were detected by immunoblot analysis with specific antisera. TNF-α treatment for 72 h significantly increased the expression of Gαi-2 and Gqα proteins and enhanced carbachol (10−7 M)-mediated inhibition of adenylyl cyclase activity and inositol phosphate synthesis. These data provide new evidence demonstrating that TNF-α not only increases expression of Gαi-2 and Gqα proteins but also augments the associated signal transduction pathways that would facilitate increased tone of airway smooth muscle.

Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

2004 ◽  
Vol 287 (6) ◽  
pp. L1230-L1240 ◽  
Author(s):  
Maria B. Sukkar ◽  
Razao Issa ◽  
Shaoping Xie ◽  
Ute Oltmanns ◽  
Robert Newton ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Tnf Α ◽  
Mrna And Protein Expression ◽  
Ifn Γ ◽  
Sb 203580

Chemokine synthesis by airway smooth muscle cells (ASMC) may be an important process underlying inflammatory cell recruitment in airway inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Fractalkine (FKN) is a recently described CX3C chemokine that has dual functions, serving as both a cell adhesion molecule and a chemoattractant for monocytes and T cells, expressing its unique receptor, CX3CR1. We investigated FKN expression by human ASMC in response to the proinflammatory cytokines IL-1β, TNF-α, and IFN-γ, the T helper 2-type cytokines IL-4, IL-10, and IL-13, and the fibrogenic cytokine transforming growth factor (TGF)-β. Neither of these cytokines alone had any significant effect on ASMC FKN production. Combined stimulation with IFN-γ and TNF-α induced FKN mRNA and protein expression in a time- and concentration-dependent manner. TGF-β had a significant inhibitory effect on cytokine-induced FKN mRNA and protein expression. Dexamethasone (10−8–10−6 M) significantly upregulated cytokine-induced FKN mRNA and protein expression. Finally, we used selective inhibitors of the mitogen-activated protein kinases c-Jun NH2-terminal kinase (JNK) (SP-610025), p38 (SB-203580), and extracellular signal-regulated kinase (PD-98095) to investigate their role in FKN production. SP-610025 (25 μM) and SB-203580 (20 μM), but not PD-98095, significantly attenuated cytokine-induced FKN protein synthesis. IFN-γ- and TNF-α-induced JNK phosphorylation remained unaltered in the presence of TGF-β but was inhibited by dexamethasone, indicating that JNK is not involved in TGF-β- or dexamethasone-mediated regulation of FKN production. In summary, FKN production by human ASMC in vitro is regulated by inflammatory and anti-inflammatory factors.

IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role of IL-4 receptor genotype

2003 ◽  
Vol 285 (4) ◽  
pp. L907-L914 ◽  
Author(s):  
Débora S. Faffe ◽  
Timothy Whitehead ◽  
Paul E. Moore ◽  
Simonetta Baraldo ◽  
Lesley Flynt ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Th2 Cells ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Tnf Α ◽  
Ifn Γ

The chemokine thymus- and activation-regulated chemokine (TARC) induces selective migration of Th2, but not Th1, lymphocytes and is upregulated in the airways of asthmatic patients. The purpose of this study was to determine whether human airway smooth muscle (HASM) cells produce TARC. Neither IL-4, IL-13, IL-1β, IFN-γ, nor TNF-α alone stimulated TARC release into the supernatant of cultured HASM cells. However, both IL-4 and IL-13 increased TARC protein and mRNA expression when administered in combination with TNF-α but not IL-1β or IFN-γ. Macrophage-derived chemokine was not expressed under any of these conditions. TARC release induced by TNF-α + IL-13 or TNF-α + IL-4 was inhibited by the β-agonist isoproterenol and by other agents that activate protein kinase A, but not by dexamethasone. To determine whether polymorphisms of the IL-4Rα have an impact on the ability of IL-13 or IL-4 to induce TARC release, HASM cells from multiple donors were genotyped for the Ile50Val, Ser478Pro, and Gln551Arg polymorphisms of the IL-4Rα. Our data indicate that cells expressing the Val50/Pro478/Arg551 haplotype had significantly greater IL-13- or IL-4-induced TARC release than cells with other IL-4Rα genotypes. These data indicate that Th2 cytokines enhance TARC expression in HASM cells in an IL-4Rα genotype-dependent fashion and suggest that airway smooth muscle cells participate in a positive feedback loop that promotes the recruitment of Th2 cells into asthmatic airways.

scholarly journals Vitamin D Attenuates TNFα‐induced Chemokine Production in Developing Human Airway Smooth Muscle Cells

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Rodney Britt ◽  
Arij Faksh ◽  
Elizabeth Vogel ◽  
Michael Thompson ◽  
Hitesh Pandya ◽  
...  
Keyword(s):  
Vitamin D ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Chemokine Production ◽  
Human Airway
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