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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

Bar plots of IRF5 (A) gene and (B) protein expression in each group. Data are expressed as the mean ± standard deviation. #P<0.01 vs. the control; *P<0.01 vs. the model. IFR5, interferon regulatory factor 5; LPS, lipopolysaccharide; IFN-γ, interferon-γ.
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f6-mmr-14-02-1091: Bar plots of IRF5 (A) gene and (B) protein expression in each group. Data are expressed as the mean ± standard deviation. #P<0.01 vs. the control; *P<0.01 vs. the model. IFR5, interferon regulatory factor 5; LPS, lipopolysaccharide; IFN-γ, interferon-γ.

Mentions: An important role for IRF5 in macrophage classical activation has been previously recognized (16,22). IRF5 is expressed at the highest levels in M1 macrophages (17,25). In the present study, macrophages in the control group expressed low gene and protein levels of IRF5, but significant increases in IRF5 gene and protein expression was observed in the model group and higher than in the control group (P<0.01; Fig. 6). Following treatment with various concentrations of mangiferin, IRF5 expression levels were significantly decreased by mangiferin at doses of 100 and 200 µmol/l (P<0.01; Fig. 6), but not at other doses. Furthermore, the decrease in 100 µmol/l mangiferin group was lower than in the 200 µmol/l group, however, there was no significant difference between the two groups (Fig. 6).


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)

Bar plots of IRF5 (A) gene and (B) protein expression in each group. Data are expressed as the mean ± standard deviation. #P<0.01 vs. the control; *P<0.01 vs. the model. IFR5, interferon regulatory factor 5; LPS, lipopolysaccharide; IFN-γ, interferon-γ.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6-mmr-14-02-1091: Bar plots of IRF5 (A) gene and (B) protein expression in each group. Data are expressed as the mean ± standard deviation. #P<0.01 vs. the control; *P<0.01 vs. the model. IFR5, interferon regulatory factor 5; LPS, lipopolysaccharide; IFN-γ, interferon-γ.
Mentions: An important role for IRF5 in macrophage classical activation has been previously recognized (16,22). IRF5 is expressed at the highest levels in M1 macrophages (17,25). In the present study, macrophages in the control group expressed low gene and protein levels of IRF5, but significant increases in IRF5 gene and protein expression was observed in the model group and higher than in the control group (P<0.01; Fig. 6). Following treatment with various concentrations of mangiferin, IRF5 expression levels were significantly decreased by mangiferin at doses of 100 and 200 µmol/l (P<0.01; Fig. 6), but not at other doses. Furthermore, the decrease in 100 µmol/l mangiferin group was lower than in the 200 µmol/l group, however, there was no significant difference between the two groups (Fig. 6).

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