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Endogenous prostaglandin E2 potentiates anti-inflammatory phenotype of macrophage through the CREB-C/EBP-β cascade
- Source :
- European Journal of Immunology. 45:2661-2671
- Publication Year :
- 2015
- Publisher :
- Wiley, 2015.
-
Abstract
- Macrophages have important functions in tissue homeostasis, but the exact mechanisms regarding wide spectrum of macrophage phenotype remain unresolved. In this study, we report that mouse bone marrow derived naïve macrophages produce prostaglandin E2 (PGE2 ) endogenously, resulting in anti-inflammatory gene expression upon differentiation induced by macrophage colony stimulating factor (M-CSF). Cyclooxygenase (COX) inhibition by indomethacin reduced endogenous PGE2 production of macrophages and subsequently reduced arg1, IL10 and Mrc1, YmI and FizzI gene expressions. Of note, PGE2 phosphorylates CREB via EP2 and EP4 receptor ligation, thereby transcriptionally increasing C/EBP-β expression in BALB/c bone marrow derived macrophages. Activated CREB directly binds to the CREB-responsive element of the C/EBP-β promoter, such that PGE2 ultimately reinforces arg1, IL10 and Mrc1 gene expression. Cyclic AMP activator forskolin also phosphorylated CREB and induced the C/EBP-β cascade, but this was completely blocked by the PKA inhibitor, H89. Consequently, M-CSF grown macrophages inhibited T-cell proliferation but the inhibition ability was reduced when the COX is inhibited by indomethacin or macrophage C/EBP-β expression was decreased by siRNA transduction. Our results collectively describe the molecular basis for homeostatic macrophage differentiation by endogenous PGE2 .
- Subjects :
- Macrophage colony-stimulating factor
medicine.medical_treatment
Prostaglandin E2 receptor
Indomethacin
Primary Cell Culture
Immunology
EP4 Receptor
Receptors, Cell Surface
Biology
CREB
Dinoprostone
Cell Line
Mice
medicine
Animals
Immunology and Allergy
Receptors, Immunologic
Prostaglandin E2
Cyclic AMP Response Element-Binding Protein
Tissue homeostasis
Sulfonamides
Membrane Glycoproteins
Arginase
Activator (genetics)
CCAAT-Enhancer-Binding Protein-beta
Macrophage Colony-Stimulating Factor
Macrophages
Colforsin
Cell Differentiation
Isoquinolines
Cyclic AMP-Dependent Protein Kinases
Interleukin-10
Cell biology
Mice, Inbred C57BL
Phenotype
Gene Expression Regulation
Prostaglandin-Endoperoxide Synthases
biology.protein
Cancer research
Female
Signal Transduction
Prostaglandin E
medicine.drug
Subjects
Details
- ISSN :
- 00142980
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- European Journal of Immunology
- Accession number :
- edsair.doi.dedup.....294bbce80dd0d9d8301fc0d52d22f40f