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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 R, Tham CL, Akhtar MN, Sulaiman MR, Israf DA - Mediators Inflamm. (2015)

Bottom Line: 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).In conclusion, these findings demonstrate the potential of DMPF-1, a nonsteroidal compound, as an antiasthmatic agent for further pharmacological evaluation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Science, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

The effect of DMPF-1 on the total and differential cell count in BALF of OVA-sensitized mice. The numbers of (a) total leukocytes and (b) eosinophils, (c) neutrophils, and (d) lymphocytes. The values are expressed as mean ± SEM (n = 10). ∗∗∗P < 0.005, significantly different from the OVA-challenged group.
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fig8: The effect of DMPF-1 on the total and differential cell count in BALF of OVA-sensitized mice. The numbers of (a) total leukocytes and (b) eosinophils, (c) neutrophils, and (d) lymphocytes. The values are expressed as mean ± SEM (n = 10). ∗∗∗P < 0.005, significantly different from the OVA-challenged group.

Mentions: As shown in Figure 8, there was a significant increment of total cell counts in BALF of OVA-challenged mice compared to naïve mice due to a significant increase in the number of infiltrating eosinophils, neutrophils, and lymphocytes. The number of inflammatory cells recruited to the lung of OVA-challenged mice in response to DMPF-1 was markedly reduced compared to that of the OVA-challenged group. Differential cell counts indicated that the changes in total cell number resulted from an increase in the representation of eosinophils as a proportion of total white blood cells in OVA-challenged mice. Administration of DMPF-1 significantly reduced the influx of inflammatory cells of all three cell types especially eosinophils in BALF in comparison to the OVA-challenged group.


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 R, Tham CL, Akhtar MN, Sulaiman MR, Israf DA - Mediators Inflamm. (2015)

The effect of DMPF-1 on the total and differential cell count in BALF of OVA-sensitized mice. The numbers of (a) total leukocytes and (b) eosinophils, (c) neutrophils, and (d) lymphocytes. The values are expressed as mean ± SEM (n = 10). ∗∗∗P < 0.005, significantly different from the OVA-challenged group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537758&req=5

fig8: The effect of DMPF-1 on the total and differential cell count in BALF of OVA-sensitized mice. The numbers of (a) total leukocytes and (b) eosinophils, (c) neutrophils, and (d) lymphocytes. The values are expressed as mean ± SEM (n = 10). ∗∗∗P < 0.005, significantly different from the OVA-challenged group.
Mentions: As shown in Figure 8, there was a significant increment of total cell counts in BALF of OVA-challenged mice compared to naïve mice due to a significant increase in the number of infiltrating eosinophils, neutrophils, and lymphocytes. The number of inflammatory cells recruited to the lung of OVA-challenged mice in response to DMPF-1 was markedly reduced compared to that of the OVA-challenged group. Differential cell counts indicated that the changes in total cell number resulted from an increase in the representation of eosinophils as a proportion of total white blood cells in OVA-challenged mice. Administration of DMPF-1 significantly reduced the influx of inflammatory cells of all three cell types especially eosinophils in BALF in comparison to the OVA-challenged group.

Bottom Line: 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).In conclusion, these findings demonstrate the potential of DMPF-1, a nonsteroidal compound, as an antiasthmatic agent for further pharmacological evaluation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Science, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus