Dexamethasone inhibits dendritic cell maturation by redirecting differentiation of a subset of cells
To investigate how corticosteroids affect differentiation of human dendritic cells (DC) in a defined inflammatory environment, we incubated immature DC with dexamethasone in the presence of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and prostaglandin E2. Dexamethasone inhibited differentiation into mature DC, as indicated by the reduced expression of antigen-presenting molecules, costimulatory and adhesion molecules, a marker of mature DC, and IL-12. Dexamethasone increased expression of CD14, CD36, and CD68, molecules characteristic of monocytes/macrophages and induced CD14+CD83- cells, a subset distinct both from immature DC and mature DC. The effects were concentration-dependent, with ID50 values between 2 and 30 nM dexamethasone. Unlike T and B cells, in DC dexamethasone induced no apoptosis, although it suppressed activated nuclear transcription factor NF-kappaB. Dexamethasone reduced the ability of DC to stimulate proliferation of allogeneic T cells in proportion to the level of CD14+CD83- cells in the population. CD83+ cells, isolated from dexamethasone-treated populations, retained the synthesis of IL-12 and the ability to stimulate proliferation of allogeneic T cells. Our data demonstrate that the dominant effect of the drug was redirecting differentiation of a subset of cells despite the presence of inflammatory cytokines. The observed ID50 values indicate that inhibition of DC differentiation might contribute significantly to in vivo immunosuppression by chronic administration of corticosteroids.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1999 |
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| Erschienen: |
1999 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:66 |
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| Enthalten in: |
Journal of leukocyte biology - 66(1999), 6 vom: 29. Dez., Seite 909-14 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Matasić, R [VerfasserIn] |
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| Anmerkungen: |
Date Completed 13.01.2000 Date Revised 15.12.2020 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM105442089 |
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| 100 | 1 | |a Matasić, R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dexamethasone inhibits dendritic cell maturation by redirecting differentiation of a subset of cells |
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| 500 | |a Date Completed 13.01.2000 | ||
| 500 | |a Date Revised 15.12.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a To investigate how corticosteroids affect differentiation of human dendritic cells (DC) in a defined inflammatory environment, we incubated immature DC with dexamethasone in the presence of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and prostaglandin E2. Dexamethasone inhibited differentiation into mature DC, as indicated by the reduced expression of antigen-presenting molecules, costimulatory and adhesion molecules, a marker of mature DC, and IL-12. Dexamethasone increased expression of CD14, CD36, and CD68, molecules characteristic of monocytes/macrophages and induced CD14+CD83- cells, a subset distinct both from immature DC and mature DC. The effects were concentration-dependent, with ID50 values between 2 and 30 nM dexamethasone. Unlike T and B cells, in DC dexamethasone induced no apoptosis, although it suppressed activated nuclear transcription factor NF-kappaB. Dexamethasone reduced the ability of DC to stimulate proliferation of allogeneic T cells in proportion to the level of CD14+CD83- cells in the population. CD83+ cells, isolated from dexamethasone-treated populations, retained the synthesis of IL-12 and the ability to stimulate proliferation of allogeneic T cells. Our data demonstrate that the dominant effect of the drug was redirecting differentiation of a subset of cells despite the presence of inflammatory cytokines. The observed ID50 values indicate that inhibition of DC differentiation might contribute significantly to in vivo immunosuppression by chronic administration of corticosteroids | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Growth Inhibitors |2 NLM | |
| 650 | 7 | |a Histocompatibility Antigens Class I |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Interleukin-1 |2 NLM | |
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| 700 | 1 | |a Dietz, A B |e verfasserin |4 aut | |
| 700 | 1 | |a Vuk-Pavlović, S |e verfasserin |4 aut | |
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