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

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.

Therapeutic Targeting of IRFs: Pathway-Dependence or Structure-Based?

“…leaves found a marked reduction in IRF5 expression in macrophages stimulated with LPS/IFNγ. This translated into a significant reduction in pro-inflammatory cytokine expression ( 136 ). How Mangiferin down-regulates IRF5 expression is not currently known.…”

An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-induced Systemic inflammatory Responses by inhibiting interferon Regulatory Factor 5 Pathway

“…Various reagents have been found to alleviate severe inflammatory reactions by interfering with IRF5. Mangiferin downregulates IRF5 expression, and therefore inhibits the activation of macrophages and the release of proinflammatory cytokines (13). Baicalin alleviates dextran sodium sulfate-induced colitis by decreasing LPS-induced IRF5 expression (14).…”

Monocytes of newly diagnosed juvenile DM1 patients are prone to differentiate into regulatory IL-10+ M2 macrophages

“…Indeed, it was previously revealed that the IRF5 gene silencing suppressed levels of IRF5 in cardiac macrophages, reprogrammed their phenotype and supported the inflammatory resolution [58]. There are also some known IRF5 inhibitors [59], like TRIM28 or KAP1 [60], flavonoids called Baicalin (which simultaneously promotes M2 phenotype by IRF4 upregulation) [61] and Quercetin [62] or polyphenol called Mangiferin [63].…”