Interleukin-1β induces MMP-9 expression via p42/p44 MAPK, p38 MAPK, JNK, and nuclear factor-κB signaling pathways in human tracheal smooth muscle cells

2007 ◽  
Vol 211 (3) ◽  
pp. 759-770 ◽  
Author(s):  
Kao-Chih Liang ◽  
Chiang-Wen Lee ◽  
Wei-Ning Lin ◽  
Chih-Chung Lin ◽  
Chou-Bin Wu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Muscle Cells ◽  
Nuclear Factor Κb ◽  
Interleukin 1Β ◽  
Tracheal Smooth Muscle ◽  
Nuclear Factor

scholarly journals Transcriptional regulation of the rat type IIA phospholipase A2 gene by cAMP and interleukin-1β in vascular smooth muscle cells: interplay of the CCAAT/enhancer binding protein (C/EBP), nuclear factor-κB and Ets transcription factors

2002 ◽  
Vol 368 (2) ◽  
pp. 415-424 ◽  
Author(s):  
Valérie ANTONIO ◽  
Arthur BROUILLET ◽  
Brigitte JANVIER ◽  
Claire MONNE ◽  
Gilbert BEREZIAT ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Phospholipase A2 ◽  
Protein C ◽  
Muscle Cells ◽  
Nuclear Factor Κb ◽  
Interleukin 1Β ◽  
Nuclear Factor ◽  
Enhancer Binding Protein ◽  
Responsive Element

The abundant secretion of type IIA secreted phospholipase A2 (sPLA2) is a major feature of the inflammatory process of atherosclerosis. sPLA2 is crucial for the development of inflammation, as it catalyses the production of lipid mediators and induces the proliferation of smooth muscle cells. We have analysed the activation of sPLA2 transcription by cAMP and interleukin-1β (IL-1β), and shown that the 500bp region upstream of the transcription start site of the rat sPLA2 gene is implicated in activation by synergistically acting cAMP and IL-1β. We transiently transfected and stimulated rat smooth muscle cells in primary culture and measured the promoter activities of serial and site-directed deletion mutants of sPLA2—luciferase constructs. A distal region, between −488 and −157 bp, bearing a CAAT/enhancer binding protein (C/EBP)-responsive element (-242 to −223) was sufficient for cAMP/protein kinase A-mediated sPLA2 promoter activation. We find evidence for the first time that activation of the sPLA2 promoter by IL-1β requires activation of an Ets-responsive element in the −184 to −180 region of the distal promoter via the Ras pathway and a nuclear factor-κB site at positions −141 to −131 of the proximal promoter. We also used electrophoretic mobility shift assays to identify five binding sites for the Sp1 factor; a specific inhibitor of Sp1, mithramycin A, showed that this factor is crucial for the basal activity of the sPLA2 promoter.

p21-activated kinase 1 participates in tracheal smooth muscle cell migration by signaling to p38 MAPK

2001 ◽  
Vol 281 (1) ◽  
pp. C123-C132 ◽  
Author(s):  
Melissa A. Dechert ◽  
Jennifer M. Holder ◽  
William T. Gerthoffer
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
P38 Mapk ◽  
Mammalian Cells ◽  
Muscle Cells ◽  
Mitogen Activated Protein Kinase ◽  
Tracheal Smooth Muscle ◽  
Wild Type ◽  
P21 Activated Kinase

Cell migration contributes to many physiological processes and requires dynamic changes in the cytoskeleton. These migration-dependent cytoskeletal changes are partly mediated by p21-activated protein kinases (PAKs). At least four closely related isoforms, PAK1, PAK2, PAK3, and PAK4, exist in mammalian cells. In smooth muscle cells, little is known about the expression, activation, or ability of PAKs to regulate migration. Our study revealed the existence of three PAK isoforms in cultured tracheal smooth muscle cells (TSMCs). Additionally, we constructed adenoviral vectors encoding wild type and a catalytically inactive PAK1 mutant to investigate PAK activation and its role in TSMC migration. Stimulation of TSMCs with platelet-derived growth factor (PDGF) increased the activity of PAK1 over time. Overexpression of mutant PAK1 blocked PDGF-induced chemotactic cell migration. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) in cells overexpressing wild-type PAK1 was similar to vector controls; however, p38 MAPK phosphorylation was severely reduced by overexpression of the PAK1 mutant. Collectively, these results suggest a role for PAK1 in chemotactic TSMC migration that involves catalytic activity and may require signaling to p38 MAPK among other pathways.

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.

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