| Title |
ISO-1, a Macrophage Migration Inhibitory Factor Antagonist, Inhibits Airway Remodeling in a Murine Model of Chronic Asthma
|
|---|---|
| Published in |
Molecular Medicine, May 2010
|
| DOI | 10.2119/molmed.2009.00128 |
| Pubmed ID | |
| Authors |
Pei-Fen Chen, Ya-ling Luo, Wei Wang, Jiang-xin Wang, Wen-yan Lai, Si-ming Hu, Kai Fan Cheng, Yousef Al-Abed |
| Abstract |
Airway remodeling is the process of airway structural change that occurs in patients with asthma in response to persistent inflammation and leads to increasing disease severity. Drugs that decrease this persistent inflammation play a crucial role in managing asthma episodes. Mice sensitized (by intraperitoneal administration) and then challenged (by inhalation) with ovalbumin (OVA) develop an extensive eosinophilic inflammatory response, goblet cell hyperplasia, collagen deposition, airway smooth muscle thickening, and airway wall area increase, similar to pathologies observed in human asthma. We used OVA-sensitized/challenged mice as a murine model of chronic allergic airway inflammation with subepithelial fibrosis (i.e., asthma). In this OVA mouse model, mRNA and protein of macrophage migration inhibitory factor (MIF) are upregulated, a response similar to what has been observed in the pathogenesis of acute inflammation in human asthma. We hypothesized that MIF induces transforming growth factor-β1 (TGF-β1) synthesis, which has been shown to play an important role in asthma and airway remodeling. To explore the role of MIF in the development of airway remodeling, we evaluated the effects of an MIF small-molecule antagonist, (S,R)3-(4-hy-droxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), on pathologies associated with the airway-remodeling process in the OVA mouse model. We found that administration of ISO-1 significantly mitigated all symptoms caused by OVA treatment. In addition, the treatment of OVA-sensitized mice with the MIF antagonist ISO-1 significantly reduced TGF-β1 mRNA levels in pulmonary tissue and its protein level in bronchial alveolar lavage fluid supernatants. We believe the repression of MIF in the ISO-1 treatment group led to the significant suppression observed in the inflammatory responses associated with the allergen-induced lung inflammation and fibrosis in our murine asthma (OVA) model. Our results implicate a possible function of MIF in the pathogenesis of chronic asthma and suggest that MIF might be an important therapeutic target for airway remodeling. |
Mendeley readers
The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Greece | 1 | 2% |
| Denmark | 1 | 2% |
| Unknown | 43 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 11 | 24% |
| Researcher | 8 | 18% |
| Other | 7 | 16% |
| Student > Doctoral Student | 3 | 7% |
| Student > Master | 3 | 7% |
| Other | 5 | 11% |
| Unknown | 8 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 14 | 31% |
| Medicine and Dentistry | 9 | 20% |
| Biochemistry, Genetics and Molecular Biology | 6 | 13% |
| Immunology and Microbiology | 3 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
| Other | 1 | 2% |
| Unknown | 11 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 April 2017.
All research outputs
#7,453,827
of 22,787,797 outputs
Outputs from Molecular Medicine
#366
of 1,135 outputs
Outputs of similar age
#34,260
of 95,260 outputs
Outputs of similar age from Molecular Medicine
#3
of 9 outputs
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