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Mangiferin inhibits macrophage classical activation via downregulating interferon regulatory factor 5 expression.

Wei Z, Yan L, Chen Y, Bao C, Deng J, Deng J - Mol Med Rep (2016)

Bottom Line: Mangiferin is a natural polyphenol and the predominant effective component of Mangifera indica Linn. leaves.The results of the present study demonstrated that mangiferin significantly inhibits LPS/IFN‑γ stimulation‑induced classical activation of macrophages in vitro and markedly decreases proinflammatory cytokine release.In addition, cellular IRF5 expression was markedly downregulated.

View Article: PubMed Central - PubMed

Affiliation: Guangxi Scientific Experimental Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P.R. China.

ABSTRACT
Mangiferin is a natural polyphenol and the predominant effective component of Mangifera indica Linn. leaves. For hundreds of years, Mangifera indica Linn. leaf has been used as an ingredient in numerous traditional Chinese medicine preparations for the treatment of bronchitis. However, the pharmacological mechanism of mangiferin in the treatment of bronchitis remains to be elucidated. Macrophage classical activation is important role in the process of bronchial airway inflammation, and interferon regulatory factor 5 (IRF5) has been identified as a key regulatory factor for macrophage classical activation. The present study used the THP‑1 human monocyte cell line to investigate whether mangiferin inhibits macrophage classical activation via suppressing IRF5 expression in vitro. THP‑1 cells were differentiated to macrophages by phorbol 12‑myristate 13‑acetate. Macrophages were polarized to M1 macrophages following stimulation with lipopolysaccharide (LPS)/interferon‑γ (IFN‑γ). Flow cytometric analysis was conducted to detect the M1 macrophages. Reverse transcription‑quantitative polymerase chain reaction was used to investigate cellular IRF5 gene expression. Levels of proinflammatory cytokines and IRF5 were assessed following cell culture and cellular homogenization using enzyme‑linked immunosorbent assay. IRF5 protein and nuclei co‑localization was performed in macrophages with laser scanning confocal microscope immunofluorescence analysis. The results of the present study demonstrated that mangiferin significantly inhibits LPS/IFN‑γ stimulation‑induced classical activation of macrophages in vitro and markedly decreases proinflammatory cytokine release. In addition, cellular IRF5 expression was markedly downregulated. These results suggest that the inhibitory effect of mangiferin on classical activation of macrophages may be exerted via downregulation of cellular IRF5 expression levels.

No MeSH data available.


Related in: MedlinePlus

Levels of TNF-α, IL-1β, IL-6 and IL-8 in the supernatant of each group. LPS/IFN-γ stimulation upregulated the levels of TNF-α, IL-1β, IL-6 and IL-8 levels in the model group. Mangiferin at doses of 100 and 200 µmol/l markedly decreased the levels of TNF-α, IL-1β, IL-6 and IL-8. Data are expressed as the mean ± standard deviation. #P<0.01 vs. the control. *P<0.01 vs. the model. TNF-α, tumor necrosis factor-α; IL, interleukin; LPS, lipopolysaccharide; IFN-γ, interferon-γ.
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f5-mmr-14-02-1091: Levels of TNF-α, IL-1β, IL-6 and IL-8 in the supernatant of each group. LPS/IFN-γ stimulation upregulated the levels of TNF-α, IL-1β, IL-6 and IL-8 levels in the model group. Mangiferin at doses of 100 and 200 µmol/l markedly decreased the levels of TNF-α, IL-1β, IL-6 and IL-8. Data are expressed as the mean ± standard deviation. #P<0.01 vs. the control. *P<0.01 vs. the model. TNF-α, tumor necrosis factor-α; IL, interleukin; LPS, lipopolysaccharide; IFN-γ, interferon-γ.

Mentions: With LPS/IFN-γ stimulation, macrophages polarized to M1 macrophages and released large quantities of proinflammatory cytokines, including TNF-α, IL-1β, IL-6 and IL-8. Thus, these proinflammatory cytokines in the supernatant can indicate the classical activation of macrophages. In the present study, the levels of TNF-α, IL-1β, IL-6 and IL-8 levels in the cell culture supernatants were increased by LPS/IFN-γ stimulation, and were significantly higher in the model group compared with the control group (P<0.01; Fig. 5). Following treatment with various concentrations of mangiferin, the TNF-α, IL-1β, IL-6 and IL-8 were significantly decreased by mangiferin at doses of 100 and 200 µmol/l (P<0.01), but not at other doses. Furthermore, the decrease in the 100 µmol/l mangiferin group was lower than in 200 µmol/l, however, there was no significant difference between the two groups (Fig. 5).


Mangiferin inhibits macrophage classical activation via downregulating interferon regulatory factor 5 expression.

Wei Z, Yan L, Chen Y, Bao C, Deng J, Deng J - Mol Med Rep (2016)

Levels of TNF-α, IL-1β, IL-6 and IL-8 in the supernatant of each group. LPS/IFN-γ stimulation upregulated the levels of TNF-α, IL-1β, IL-6 and IL-8 levels in the model group. Mangiferin at doses of 100 and 200 µmol/l markedly decreased the levels of TNF-α, IL-1β, IL-6 and IL-8. Data are expressed as the mean ± standard deviation. #P<0.01 vs. the control. *P<0.01 vs. the model. TNF-α, tumor necrosis factor-α; IL, interleukin; LPS, lipopolysaccharide; IFN-γ, interferon-γ.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940072&req=5

f5-mmr-14-02-1091: Levels of TNF-α, IL-1β, IL-6 and IL-8 in the supernatant of each group. LPS/IFN-γ stimulation upregulated the levels of TNF-α, IL-1β, IL-6 and IL-8 levels in the model group. Mangiferin at doses of 100 and 200 µmol/l markedly decreased the levels of TNF-α, IL-1β, IL-6 and IL-8. Data are expressed as the mean ± standard deviation. #P<0.01 vs. the control. *P<0.01 vs. the model. TNF-α, tumor necrosis factor-α; IL, interleukin; LPS, lipopolysaccharide; IFN-γ, interferon-γ.
Mentions: With LPS/IFN-γ stimulation, macrophages polarized to M1 macrophages and released large quantities of proinflammatory cytokines, including TNF-α, IL-1β, IL-6 and IL-8. Thus, these proinflammatory cytokines in the supernatant can indicate the classical activation of macrophages. In the present study, the levels of TNF-α, IL-1β, IL-6 and IL-8 levels in the cell culture supernatants were increased by LPS/IFN-γ stimulation, and were significantly higher in the model group compared with the control group (P<0.01; Fig. 5). Following treatment with various concentrations of mangiferin, the TNF-α, IL-1β, IL-6 and IL-8 were significantly decreased by mangiferin at doses of 100 and 200 µmol/l (P<0.01), but not at other doses. Furthermore, the decrease in the 100 µmol/l mangiferin group was lower than in 200 µmol/l, however, there was no significant difference between the two groups (Fig. 5).

Bottom Line: Mangiferin is a natural polyphenol and the predominant effective component of Mangifera indica Linn. leaves.The results of the present study demonstrated that mangiferin significantly inhibits LPS/IFN‑γ stimulation‑induced classical activation of macrophages in vitro and markedly decreases proinflammatory cytokine release.In addition, cellular IRF5 expression was markedly downregulated.

View Article: PubMed Central - PubMed

Affiliation: Guangxi Scientific Experimental Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P.R. China.

ABSTRACT
Mangiferin is a natural polyphenol and the predominant effective component of Mangifera indica Linn. leaves. For hundreds of years, Mangifera indica Linn. leaf has been used as an ingredient in numerous traditional Chinese medicine preparations for the treatment of bronchitis. However, the pharmacological mechanism of mangiferin in the treatment of bronchitis remains to be elucidated. Macrophage classical activation is important role in the process of bronchial airway inflammation, and interferon regulatory factor 5 (IRF5) has been identified as a key regulatory factor for macrophage classical activation. The present study used the THP‑1 human monocyte cell line to investigate whether mangiferin inhibits macrophage classical activation via suppressing IRF5 expression in vitro. THP‑1 cells were differentiated to macrophages by phorbol 12‑myristate 13‑acetate. Macrophages were polarized to M1 macrophages following stimulation with lipopolysaccharide (LPS)/interferon‑γ (IFN‑γ). Flow cytometric analysis was conducted to detect the M1 macrophages. Reverse transcription‑quantitative polymerase chain reaction was used to investigate cellular IRF5 gene expression. Levels of proinflammatory cytokines and IRF5 were assessed following cell culture and cellular homogenization using enzyme‑linked immunosorbent assay. IRF5 protein and nuclei co‑localization was performed in macrophages with laser scanning confocal microscope immunofluorescence analysis. The results of the present study demonstrated that mangiferin significantly inhibits LPS/IFN‑γ stimulation‑induced classical activation of macrophages in vitro and markedly decreases proinflammatory cytokine release. In addition, cellular IRF5 expression was markedly downregulated. These results suggest that the inhibitory effect of mangiferin on classical activation of macrophages may be exerted via downregulation of cellular IRF5 expression levels.

No MeSH data available.


Related in: MedlinePlus