Inhibition of epithelial CC-family chemokine synthesis by the synthetic chalcone DMPF-1 via disruption of NF-κB nuclear translocation and suppression of experimental asthma in mice
Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The interaction between airway epithelium and inflammatory mediators plays a key role in the pathogenesis of asthma. In vitro studies evaluated the inhibitory effects of 3-(2,5-dimethoxyphenyl)-1-(5-methylfura...
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| Format: | Article |
| Language: | English |
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Hindawi Publishing Corporation
2015
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| Online Access: | http://psasir.upm.edu.my/id/eprint/34211/ http://psasir.upm.edu.my/id/eprint/34211/1/Inhibition%20of%20Epithelial%20CC-Family%20Chemokine.pdf |
| _version_ | 1848847707142094848 |
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| author | Rajajendram, Revathee Tham, Chau Ling Akhtar, Mohamad Nadeem Sulaiman, Mohd Roslan Israf Ali, Daud Ahmad |
| author_facet | Rajajendram, Revathee Tham, Chau Ling Akhtar, Mohamad Nadeem Sulaiman, Mohd Roslan Israf Ali, Daud Ahmad |
| author_sort | Rajajendram, Revathee |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The interaction between airway epithelium and inflammatory mediators plays a key role in the pathogenesis of asthma. In vitro studies evaluated the inhibitory effects of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMPF-1), a synthetic chalcone analogue, upon inflammation in the A549 lung epithelial cell line. DMPF-1 selectively inhibited TNF-α-stimulated CC chemokine secretion (RANTES, eotaxin-1, and MCP-1) without any effect upon CXC chemokine (GRO-α and IL-8) secretion. Western blot analysis further demonstrated that the inhibitory activity resulted from disruption of p65NF-κB nuclear translocation without any effects on the mitogen-activated protein kinase (MAPK) pathway. Treatment of ovalbumin-sensitized and ovalbumin-challenged BALB/c mice with DMPF-1 (0.2–100 mg/kg) demonstrated significant reduction in the secretion and gene expression of CC chemokines (RANTES, eotaxin-1, and MCP-1) and Th2 cytokines (IL-4, IL-5, and IL-13). Furthermore, DMPF-1 treatment inhibited eosinophilia, goblet cell hyperplasia, peripheral blood total IgE, and airway hyperresponsiveness in ovalbumin-sensitized and ovalbumin-challenged mice. In conclusion, these findings demonstrate the potential of DMPF-1, a nonsteroidal compound, as an antiasthmatic agent for further pharmacological evaluation. |
| first_indexed | 2025-11-15T09:22:53Z |
| format | Article |
| id | upm-34211 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T09:22:53Z |
| publishDate | 2015 |
| publisher | Hindawi Publishing Corporation |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-342112015-12-09T03:37:53Z http://psasir.upm.edu.my/id/eprint/34211/ Inhibition of epithelial CC-family chemokine synthesis by the synthetic chalcone DMPF-1 via disruption of NF-κB nuclear translocation and suppression of experimental asthma in mice Rajajendram, Revathee Tham, Chau Ling Akhtar, Mohamad Nadeem Sulaiman, Mohd Roslan Israf Ali, Daud Ahmad Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The interaction between airway epithelium and inflammatory mediators plays a key role in the pathogenesis of asthma. In vitro studies evaluated the inhibitory effects of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMPF-1), a synthetic chalcone analogue, upon inflammation in the A549 lung epithelial cell line. DMPF-1 selectively inhibited TNF-α-stimulated CC chemokine secretion (RANTES, eotaxin-1, and MCP-1) without any effect upon CXC chemokine (GRO-α and IL-8) secretion. Western blot analysis further demonstrated that the inhibitory activity resulted from disruption of p65NF-κB nuclear translocation without any effects on the mitogen-activated protein kinase (MAPK) pathway. Treatment of ovalbumin-sensitized and ovalbumin-challenged BALB/c mice with DMPF-1 (0.2–100 mg/kg) demonstrated significant reduction in the secretion and gene expression of CC chemokines (RANTES, eotaxin-1, and MCP-1) and Th2 cytokines (IL-4, IL-5, and IL-13). Furthermore, DMPF-1 treatment inhibited eosinophilia, goblet cell hyperplasia, peripheral blood total IgE, and airway hyperresponsiveness in ovalbumin-sensitized and ovalbumin-challenged mice. In conclusion, these findings demonstrate the potential of DMPF-1, a nonsteroidal compound, as an antiasthmatic agent for further pharmacological evaluation. Hindawi Publishing Corporation 2015 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/34211/1/Inhibition%20of%20Epithelial%20CC-Family%20Chemokine.pdf Rajajendram, Revathee and Tham, Chau Ling and Akhtar, Mohamad Nadeem and Sulaiman, Mohd Roslan and Israf Ali, Daud Ahmad (2015) Inhibition of epithelial CC-family chemokine synthesis by the synthetic chalcone DMPF-1 via disruption of NF-κB nuclear translocation and suppression of experimental asthma in mice. Mediators of Inflammation, 2015. art. no. 176926. pp. 1-14. ISSN 0962-9351; ESSN: 1466-1861 http://www.hindawi.com/journals/mi/2015/176926/abs/ 10.1155/2015/176926 |
| spellingShingle | Rajajendram, Revathee Tham, Chau Ling Akhtar, Mohamad Nadeem Sulaiman, Mohd Roslan Israf Ali, Daud Ahmad Inhibition of epithelial CC-family chemokine synthesis by the synthetic chalcone DMPF-1 via disruption of NF-κB nuclear translocation and suppression of experimental asthma in mice |
| title | Inhibition of epithelial CC-family chemokine synthesis by the synthetic chalcone DMPF-1 via disruption of NF-κB nuclear translocation and suppression of experimental asthma in mice |
| title_full | Inhibition of epithelial CC-family chemokine synthesis by the synthetic chalcone DMPF-1 via disruption of NF-κB nuclear translocation and suppression of experimental asthma in mice |
| title_fullStr | Inhibition of epithelial CC-family chemokine synthesis by the synthetic chalcone DMPF-1 via disruption of NF-κB nuclear translocation and suppression of experimental asthma in mice |
| title_full_unstemmed | Inhibition of epithelial CC-family chemokine synthesis by the synthetic chalcone DMPF-1 via disruption of NF-κB nuclear translocation and suppression of experimental asthma in mice |
| title_short | Inhibition of epithelial CC-family chemokine synthesis by the synthetic chalcone DMPF-1 via disruption of NF-κB nuclear translocation and suppression of experimental asthma in mice |
| title_sort | inhibition of epithelial cc-family chemokine synthesis by the synthetic chalcone dmpf-1 via disruption of nf-κb nuclear translocation and suppression of experimental asthma in mice |
| url | http://psasir.upm.edu.my/id/eprint/34211/ http://psasir.upm.edu.my/id/eprint/34211/ http://psasir.upm.edu.my/id/eprint/34211/ http://psasir.upm.edu.my/id/eprint/34211/1/Inhibition%20of%20Epithelial%20CC-Family%20Chemokine.pdf |