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Published on: May 31, 2018
Pigment epithelium-derived factor induces interleukin-10 expression in human macrophages by induction of PPAR gamma
Su-Lin Yang1, Show-Li Chen, Ju-Yun Wu
1Centers for Disease Control, Taiwan.
Aim:
In search for the anti-inflammation mechanism of PEDF, we investigate whether pigment epithelium-derived factor (PEDF) induces the gene expression of interleukin (IL)-10 in human macrophages and determine the molecular basis of this induction.
Main Methods:
Human macrophages derived from a monocytic cell line, THP-1, and peripheral monocytes were treated with PEDF. IL-10 expression was assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, semi-quantitative reverse transcriptase (RT)-PCR, and promoter-reporter assay. Activity of extracellular signal-regulated kinase 2 (ERK2) and p38 mitogen-activated protein kinase (MAPK) was assessed by immunoblotting using antibodies targeting phosphorylated kinases forms. Elk-1 and ATF-2 phosphorylation was determined as well. Pharmacological inhibitors were used to examine the involvement of ERK, p38 MAPK, and peroxisome proliferator-activated receptor gamma (PPARgamma) on the IL-10 expression induced by PEDF.
Key Findings:
PEDF increased the levels of IL-10 mRNA and protein in THP-1 cells and human macrophages derived from peripheral monocytes. Blockade of activity of ERK or p38 MAPK attenuated PEDF effects on induction of PPARgamma and IL-10. PEDF increased the transcriptional activity of IL-10 promoter. The effect was synergistically augmented by PPARgamma agonist, but attenuated by inhibitors of PPARgamma, ERK or p38 MAPK. These results showed that PEDF promotes IL-10 expression at transcriptional level, and that this is achieved through the ERK2/p38MAPK-dependent PPARgamma expression.
Significance:
The anti-inflammatory property of PEDF may in part through the induction of IL-10 in macrophages. Our study supports the therapeutic potential of PEDF and PPARgamma agonists in inflammatory diseases.
Insights
Pigment epithelium-derived factor (PEDF) induces anti-inflammatory interleukin-10 (IL-10) in macrophages. This occurs via the ERK2/p38MAPK-dependent pathway, highlighting PEDF
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Inflammation is a key component of many diseases.
- Interleukin-10 (IL-10) is a crucial anti-inflammatory cytokine.
- Pigment epithelium-derived factor (PEDF) has demonstrated anti-inflammatory properties.
Purpose of the Study:
- To investigate the anti-inflammatory mechanism of PEDF.
- To determine if PEDF induces IL-10 gene expression in human macrophages.
- To elucidate the molecular basis of PEDF-induced IL-10 expression.
Main Methods:
- Human macrophages (THP-1 cell line and peripheral monocytes) were treated with PEDF.
- IL-10 mRNA and protein levels were measured using qRT-PCR and ELISA.
- Signaling pathways involving ERK, p38 MAPK, and PPARgamma were analyzed using inhibitors and reporter assays.
Main Results:
- PEDF significantly increased IL-10 mRNA and protein levels in macrophages.
- PEDF-induced IL-10 expression was dependent on ERK and p38 MAPK activation.
- PEDF promoted IL-10 transcription through the ERK2/p38MAPK-dependent PPARgamma pathway.
Conclusions:
- PEDF exerts anti-inflammatory effects partly by inducing IL-10 in macrophages.
- The findings support the therapeutic potential of PEDF and PPARgamma agonists for inflammatory conditions.
