Academic Journal
Protein kinase A inhibition of macrophage maturation is accompanied by an increase in DNA methylation of the colony‐stimulating factor 1 receptor gene
| العنوان: | Protein kinase A inhibition of macrophage maturation is accompanied by an increase in DNA methylation of the colony‐stimulating factor 1 receptor gene |
|---|---|
| المؤلفون: | Zasłona, Zbigniew, Scruggs, Anne M., Peters‐Golden, Marc, Huang, Steven K. |
| المساهمون: | American Lung Association, National Heart, Lung, and Blood Institute |
| المصدر: | Immunology ; volume 149, issue 2, page 225-237 ; ISSN 0019-2805 1365-2567 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2016 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Summary Macrophage colony‐stimulating factor 1 ( CSF ‐1) plays a critical role in the differentiation of mononuclear phagocytes from bone marrow precursors, and maturing monocytes and macrophages exhibit increased expression of the CSF ‐1 receptor, CSF 1R. The expression of CSF 1R is tightly regulated by transcription factors and epigenetic mechanisms. We previously showed that prostaglandin E 2 and subsequent activation of protein kinase A ( PKA ) inhibited CSF 1R expression and macrophage maturation. Here, we examine the DNA methylation changes that occur at the Csf1r locus during macrophage maturation in the presence or absence of activated PKA . Murine bone marrow cells were matured to macrophages by incubating cells with CSF ‐1‐containing conditioned medium for up to 6 days in the presence or absence of the PKA agonist 6‐bnz‐ cAMP . DNA methylation of Csf1r promoter and enhancer regions was assayed by bisulphite pyrosequencing. DNA methylation of Csf1r decreased during normal macrophage maturation in concert with an increase in Csf1r mRNA expression. Treatment with the PKA agonist inhibited Csf1r mRNA and protein expression, and increased DNA methylation at the Csf1r promoter. This was associated with decreased binding of the transcription factor PU .1 to the Csf1r promoter. Treatment with the PKA agonist inhibited the responsiveness of macrophages to CSF ‐1. Levels of endogenous PKA activity decreased during normal macrophage maturation, suggesting that attenuation of this signalling pathway contributes to the increase in CSF 1R expression during macrophage maturation. Together, these results demonstrate that macrophage maturation is accompanied by Csf1r hypomethylation, and illustrates for the first time the ability of PKA to increase Csf1r DNA methylation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/imm.12641 |
| الاتاحة: | http://dx.doi.org/10.1111/imm.12641 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fimm.12641 https://onlinelibrary.wiley.com/doi/pdf/10.1111/imm.12641 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.DC0E5E6B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/imm.12641 |
|---|