New perspectives on mechanisms underlying chronic allergic inflammation and asthma in 2007

Broide, David H.

doi:10.1016/j.jaci.2008.06.025

Cited by 26 publications

(26 citation statements)

References 64 publications

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“…Literature precedent and analysis with Genomatix MatInspector identified three AP-1 sites, 298/291 (AP-1 [1]), 2552/2545 (AP-1 [2]), 21671/21664 (AP-1 [3]), conforming to the 12-O-tetradecanoylphorbol-13-acetate response element (TRE) or AP-1 consensus sequence 59-TGA(C/G)TCA-39 within the 21723/26 MMP-9 promoter region (28,29) (Fig. 1A).…”

Section: Promoter Constructs and Transfection And Luciferase Assaysmentioning

confidence: 99%

“…1A). Point mutations within the two proximal AP-1 sites at 298/291 bp (mAP-1 [1]) and 2552/ 2545 bp (mAP-1 [2]) were introduced using site-directed mutagenesis within the 21017/26 bp MMP-9 promoter luciferase construct. Forward primer sequences were as follows, with mutated residues depicted as lowercase letters: mAP-1 [1] 59-CTGACCCCTGAGTtgGCACTTGCCT-39 and mAP-1 [2] 59-AGAGGAAGCTGAGTtgAAGAAGGCT-39 (30).…”

Section: Promoter Constructs and Transfection And Luciferase Assaysmentioning

confidence: 99%

“…A double-stranded oligonucleotide containing an AP-1 transcription factor binding site with the identical consensus sequence to the two proximal AP-1 sites, but identical to the identical flanking sequence to the AP-1 [1] site (underlined, 59-CTGACCCCTGAGTCAGCACTTGCCT-39), was used for EMSA and supershift assays as described previously (31). The modulation of Fra-1 AP-1 DNA binding was investigated using a TransAM kit containing a generic AP-1 consensus sequence that was identical to the consensus sequence present in both the AP-1 [1] and AP-1 [2] sites. Briefly, 10-15 mg nuclear extract was loaded onto 96-well plates precoated with oligonucleotides containing the AP-1 consensus sequence.…”

Section: Promoter Constructs and Transfection And Luciferase Assaysmentioning

confidence: 99%

“…Data from our previous publication established that the AP-1 [3] site was not necessary for HRV-induced MMP-9 expression (13). We therefore synthesized luciferase promoter constructs in which mutations were introduced in one or both of the AP-1 [1] or AP-1 [2] sites: mAP-1 [1], mAP-1 [2], and mAP-1 [1,2], respectively. Mutation of the AP-1 [1] site reduced both control basal and virally induced promoter drive relative to the 21017/26 bp wildtype construct (Fig.…”

Section: Ap-1 Is Necessary For Hrv-induced Mmp-9 Transcriptionmentioning

confidence: 99%

“…A irway inflammation and airway remodeling are characteristic features of asthma (1,2). Together, they are thought to contribute to the pathophysiology of airway hyperresponsiveness, which is the clinical hallmark of the disease (3).…”

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Rhinovirus-Induced MMP-9 Expression Is Dependent on Fra-1, Which Is Modulated by Formoterol and Dexamethasone

Tacon

Newton

Leigh

2012

The Journal of Immunology

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Matrix metalloproteinase-9 is implicated in airway inflammation and airway remodeling in asthma. We have previously confirmed that human rhinovirus-16 (HRV-16) infection increases MMP-9 expression both in vivo and in vitro. However, the role of the AP-1 sites within the MMP-9 promoter and the effect of commonly used asthma pharmacotherapies in modulating human rhinovirus (HRV)-induced MMP-9 production have not yet been elucidated. Experiments were performed in vitro in the human bronchial epithelial (HBE) cell line BEAS-2B and in primary HBE cells obtained from non-transplanted lungs. Using site-directed mutagenesis approaches, AP-1 sites were found to be necessary for HRV-induced MMP-9 promoter drive. EMSAs and supershift assays identified complexes consisting of Fos-related Ag-1 (Fra-1) in addition to other AP-1 subunits. Small interfering RNA approaches indicated that Fra-1 was induced upon HRV-16 infection in BEAS-2B cells and was necessary for MMP-9 expression in both BEAS-2B and primary HBE cells. Inhibition of MEK1/2 activity using PD98059 and U0126 reduced Fra-1 expression, DNA binding, MMP-9 promoter drive, and MMP-9 protein production. The long-acting β2-agonist formoterol and the glucocorticoid dexamethasone significantly reduced HRV-induced ERK phosphorylation, Fra-1, and MMP-9 expression in BEAS-2B cells. These data indicate that HRV-induced activation of the MEK/ERK MAPK pathway and Fra-1 expression are necessary for the upregulation of MMP-9 and can be modulated by two distinct but commonly used asthma pharmacotherapies. Together, these results offer insights into the mechanisms by which long-acting β2-agonists and glucocorticoids might reduce HRV-related asthma exacerbations.

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Section: Promoter Constructs and Transfection And Luciferase Assaysmentioning

confidence: 99%

Section: Promoter Constructs and Transfection And Luciferase Assaysmentioning

confidence: 99%

Section: Promoter Constructs and Transfection And Luciferase Assaysmentioning

confidence: 99%

Section: Ap-1 Is Necessary For Hrv-induced Mmp-9 Transcriptionmentioning

confidence: 99%

mentioning

confidence: 99%

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Rhinovirus-Induced MMP-9 Expression Is Dependent on Fra-1, Which Is Modulated by Formoterol and Dexamethasone

Tacon

Newton

Leigh

2012

The Journal of Immunology

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A novel strategy for development of glucocorticoids through non-genomic mechanism

Zhou

Sheng

et al. 2010

Cell. Mol. Life Sci.

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Glucocorticoids (GCs) are routinely believed to take effect through genomic mechanisms, which are also largely responsible for GCs' side effects. Beneficial non-genomic effects of GCs have been reported as being independent of the genomic pathway. Here, we synthesized a new type of GCs, which took effect mainly via non-genomic mechanisms. Hydrocortisone was conjugated with glycine, lysine and phenylalanine to get a bigger molecular structure, which could hardly go through the cell membrane. Evaluation of the anti-inflammatory efficacy showed that hydrocortisone-conjugated glycine (HG) and lysine could inhibit neutrophil degranulation within 15 min. HG could inhibit IgE-mediated histamine release from mast cells via a non-genomic pathway, and rapidly alleviate allergic reaction. Luciferase reporter assay showed that HG would not activate the glucocorticoid response element within 30 min, which verified the rapid effects independent of the genomic pathway. The work proposes a novel insight into the development of novel GCs, and provides new tools for experimental study on non-genomic mechanisms.

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Effects of a high-fat meal on pulmonary function in healthy subjects

et al. 2010

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Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.

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New perspectives on mechanisms underlying chronic allergic inflammation and asthma in 2007

Cited by 26 publications

References 64 publications

Rhinovirus-Induced MMP-9 Expression Is Dependent on Fra-1, Which Is Modulated by Formoterol and Dexamethasone

Rhinovirus-Induced MMP-9 Expression Is Dependent on Fra-1, Which Is Modulated by Formoterol and Dexamethasone

A novel strategy for development of glucocorticoids through non-genomic mechanism

Effects of a high-fat meal on pulmonary function in healthy subjects

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