Pigment epithelium-derived factor induces interleukin-10 expression in human macrophages by induction of PPAR gamma
Journal
Life Sciences
Journal Volume
87
Journal Issue
1/2
Pages
26-35
Date Issued
2010
Author(s)
Abstract
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 (PPARγ) 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 PPARγ and IL-10. PEDF increased the transcriptional activity of IL-10 promoter. The effect was synergistically augmented by PPARγ agonist, but attenuated by inhibitors of PPARγ, 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 PPARγ 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 PPARγ agonists in inflammatory diseases. ? 2010 Elsevier Inc.
Subjects
Anti-inflammation; MAPK signaling; PPREs; Transcriptional regulation
SDGs
Other Subjects
2 (2 amino 3 methoxyphenyl)chromone; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; activating transcription factor 2; anthra[1,9 cd]pyrazol 6(2h) one; ciglitazone; cycloheximide; gamma interferon; interleukin 10; interleukin 12p40; interleukin 6; mitogen activated protein kinase 1; mitogen activated protein kinase p38; peroxisome proliferator activated receptor gamma; pigment epithelium derived factor; transcription factor Elk 1; tumor necrosis factor alpha; antiinflammatory activity; article; controlled study; enzyme linked immunosorbent assay; gene expression; human; human cell; macrophage; protein phosphorylation; real time polymerase chain reaction; reverse transcription polymerase chain reaction; transcription regulation; Cell Line; Enzyme-Linked Immunosorbent Assay; Eye Proteins; Gene Expression Regulation; Genes, Reporter; Humans; Immunoblotting; Interleukin-10; Macrophages; Mitogen-Activated Protein Kinase 1; Nerve Growth Factors; p38 Mitogen-Activated Protein Kinases; Polymerase Chain Reaction; PPAR gamma; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Serpins; Transcription, Genetic
Type
journal article