Cisplatin at clinically relevant concentrations enhances interleukin-2 synthesis by human primary blood lymphocytes
Riesbeck, Kristian LU
(1999)
In Anti-Cancer Drugs
10(2).
p.219-227
- Abstract
Cytotoxic drugs influence the expression of certain genes in cancer cells. Cisplatin has recently been shown to modulate interleukin (IL)-1 and tumor necrosis factor (TNF)-α production in macrophages. In this study, we wanted to investigate whether cisplatin interferes with the IL-2, IL-2 receptor (IL-2R), interferon (IFN)-γ, and TNF-α expression in phytohemagglutin-stimulated human peripheral blood lymphocytes. IL-2 was analyzed in a bioassay, while IFN-γ and TNF-α were measured by ELISA. Northern blots were performed to quantify steady-state cytokine mRNA levels. Furthermore, T cell subsets and IL-2R surface expression were analyzed by means of flow cytometry. A maximum stimulatory effect on IL-2 production (1.8-fold increase) was... (More)
Cytotoxic drugs influence the expression of certain genes in cancer cells. Cisplatin has recently been shown to modulate interleukin (IL)-1 and tumor necrosis factor (TNF)-α production in macrophages. In this study, we wanted to investigate whether cisplatin interferes with the IL-2, IL-2 receptor (IL-2R), interferon (IFN)-γ, and TNF-α expression in phytohemagglutin-stimulated human peripheral blood lymphocytes. IL-2 was analyzed in a bioassay, while IFN-γ and TNF-α were measured by ELISA. Northern blots were performed to quantify steady-state cytokine mRNA levels. Furthermore, T cell subsets and IL-2R surface expression were analyzed by means of flow cytometry. A maximum stimulatory effect on IL-2 production (1.8-fold increase) was observed with cisplatin at 5-10 μM while IFN-γ and TNF-α synthesis and IL-2R density were unaffected. However, cisplatin-treated cells displayed enhanced IL-2, IL-2R, IFN-γ and TNF-α mRNA levels compared to drug-free controls. Cisplatin did not prolong cytokine mRNA half-life as revealed with the transcriptional inhibitor actinomycin D. In contrast to an inhibited growth of CD4+ T lymphocytes, CD3+CD8+ cell density was unaffected at intermediate cisplatin concentrations (10 μM). Bleomycin, carboplatin, doxorubicin, novobiocin or etoposide, which were included for comparison, did not interfere with IL-2 expression. Our data imply that cisplatin most likely stimulated cytokine transcription via a putative stress induced signaling pathway.
(Less)
- author
- Riesbeck, Kristian
LU
- organization
- publishing date
- 1999-01-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cisplatin, Cytokines, DNA damage response, Interleukin-2, Peripheral blood lymphocytes
- in
- Anti-Cancer Drugs
- volume
- 10
- issue
- 2
- pages
- 219 - 227
- publisher
- Rapid Communications
- external identifiers
-
- scopus:0033034870
- pmid:10211553
- ISSN
- 0959-4973
- language
- English
- LU publication?
- yes
- id
- d663fd4b-b7c4-4b43-a435-9b2db21672c5
- alternative location
- https://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=1999&issue=02000&article=00011&type=abstract
- date added to LUP
- 2019-06-07 15:17:08
- date last changed
- 2024-01-01 09:33:39
@article{d663fd4b-b7c4-4b43-a435-9b2db21672c5,
abstract = {{<p>Cytotoxic drugs influence the expression of certain genes in cancer cells. Cisplatin has recently been shown to modulate interleukin (IL)-1 and tumor necrosis factor (TNF)-α production in macrophages. In this study, we wanted to investigate whether cisplatin interferes with the IL-2, IL-2 receptor (IL-2R), interferon (IFN)-γ, and TNF-α expression in phytohemagglutin-stimulated human peripheral blood lymphocytes. IL-2 was analyzed in a bioassay, while IFN-γ and TNF-α were measured by ELISA. Northern blots were performed to quantify steady-state cytokine mRNA levels. Furthermore, T cell subsets and IL-2R surface expression were analyzed by means of flow cytometry. A maximum stimulatory effect on IL-2 production (1.8-fold increase) was observed with cisplatin at 5-10 μM while IFN-γ and TNF-α synthesis and IL-2R density were unaffected. However, cisplatin-treated cells displayed enhanced IL-2, IL-2R, IFN-γ and TNF-α mRNA levels compared to drug-free controls. Cisplatin did not prolong cytokine mRNA half-life as revealed with the transcriptional inhibitor actinomycin D. In contrast to an inhibited growth of CD4<sup>+</sup> T lymphocytes, CD3<sup>+</sup>CD8<sup>+</sup> cell density was unaffected at intermediate cisplatin concentrations (10 μM). Bleomycin, carboplatin, doxorubicin, novobiocin or etoposide, which were included for comparison, did not interfere with IL-2 expression. Our data imply that cisplatin most likely stimulated cytokine transcription via a putative stress induced signaling pathway.</p>}},
author = {{Riesbeck, Kristian}},
issn = {{0959-4973}},
keywords = {{Cisplatin; Cytokines; DNA damage response; Interleukin-2; Peripheral blood lymphocytes}},
language = {{eng}},
month = {{01}},
number = {{2}},
pages = {{219--227}},
publisher = {{Rapid Communications}},
series = {{Anti-Cancer Drugs}},
title = {{Cisplatin at clinically relevant concentrations enhances interleukin-2 synthesis by human primary blood lymphocytes}},
url = {{https://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=1999&issue=02000&article=00011&type=abstract}},
volume = {{10}},
year = {{1999}},
}