Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation
Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of dec...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/4/868 |
| _version_ | 1797538043972812800 |
|---|---|
| author | Fabiana Albani Zambuzi Priscilla Mariane Cardoso-Silva Ricardo Cardoso Castro Caroline Fontanari Flavio da Silva Emery Fabiani Gai Frantz |
| author_facet | Fabiana Albani Zambuzi Priscilla Mariane Cardoso-Silva Ricardo Cardoso Castro Caroline Fontanari Flavio da Silva Emery Fabiani Gai Frantz |
| author_sort | Fabiana Albani Zambuzi |
| collection | DOAJ |
| description | Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to <i>Mycobacterium tuberculosis</i> in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response. |
| first_indexed | 2024-03-10T12:24:52Z |
| format | Article |
| id | doaj.art-2910964f3700435297c4e30e985ceeee |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:24:52Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2910964f3700435297c4e30e985ceeee2023-11-21T15:07:23ZengMDPI AGCells2073-44092021-04-0110486810.3390/cells10040868Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response RegulationFabiana Albani Zambuzi0Priscilla Mariane Cardoso-Silva1Ricardo Cardoso Castro2Caroline Fontanari3Flavio da Silva Emery4Fabiani Gai Frantz5Faculdade de Ciências Farmacêuticas de Ribeirão Preto–FCFRP-USP, Ribeirão Preto, São Paulo 14041-903, BrazilFaculdade de Ciências Farmacêuticas de Ribeirão Preto–FCFRP-USP, Ribeirão Preto, São Paulo 14041-903, BrazilFaculdade de Ciências Farmacêuticas de Ribeirão Preto–FCFRP-USP, Ribeirão Preto, São Paulo 14041-903, BrazilFaculdade de Ciências Farmacêuticas de Ribeirão Preto–FCFRP-USP, Ribeirão Preto, São Paulo 14041-903, BrazilFaculdade de Ciências Farmacêuticas de Ribeirão Preto–FCFRP-USP, Ribeirão Preto, São Paulo 14041-903, BrazilFaculdade de Ciências Farmacêuticas de Ribeirão Preto–FCFRP-USP, Ribeirão Preto, São Paulo 14041-903, BrazilDecitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to <i>Mycobacterium tuberculosis</i> in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.https://www.mdpi.com/2073-4409/10/4/868DNMT inhibitorsphagocytosisimmune cellmonocyte/macrophages |
| spellingShingle | Fabiana Albani Zambuzi Priscilla Mariane Cardoso-Silva Ricardo Cardoso Castro Caroline Fontanari Flavio da Silva Emery Fabiani Gai Frantz Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation Cells DNMT inhibitors phagocytosis immune cell monocyte/macrophages |
| title | Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation |
| title_full | Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation |
| title_fullStr | Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation |
| title_full_unstemmed | Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation |
| title_short | Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation |
| title_sort | decitabine promotes modulation in phenotype and function of monocytes and macrophages that drive immune response regulation |
| topic | DNMT inhibitors phagocytosis immune cell monocyte/macrophages |
| url | https://www.mdpi.com/2073-4409/10/4/868 |
| work_keys_str_mv | AT fabianaalbanizambuzi decitabinepromotesmodulationinphenotypeandfunctionofmonocytesandmacrophagesthatdriveimmuneresponseregulation AT priscillamarianecardososilva decitabinepromotesmodulationinphenotypeandfunctionofmonocytesandmacrophagesthatdriveimmuneresponseregulation AT ricardocardosocastro decitabinepromotesmodulationinphenotypeandfunctionofmonocytesandmacrophagesthatdriveimmuneresponseregulation AT carolinefontanari decitabinepromotesmodulationinphenotypeandfunctionofmonocytesandmacrophagesthatdriveimmuneresponseregulation AT flaviodasilvaemery decitabinepromotesmodulationinphenotypeandfunctionofmonocytesandmacrophagesthatdriveimmuneresponseregulation AT fabianigaifrantz decitabinepromotesmodulationinphenotypeandfunctionofmonocytesandmacrophagesthatdriveimmuneresponseregulation |