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Ciprofloxacin induces an immunomodulatory stress response in human T lymphocytes

Riesbeck, Kristian LU ; Forsgren, Arne LU ; Henriksson, Agnethe and Bredberg, Anders LU (1998) In Antimicrobial Agents and Chemotherapy 42(8). p.1923-1930
Abstract

Exposure of cells to adverse environmental conditions invokes a genetically programmed series of events resulting in the induction of specific genes. The fluoroquinolone antibiotic ciprofloxacin has recently been reported to upregulate interleukin-2 (IL-2) gene induction. In the present investigation, the effect of ciprofloxacin at supratherapeutic concentrations on immediate-early (<2 h) gene expression in primary human peripheral blood lymphocytes was studied with Northern blots. In addition, transcriptional activity of IL-2 and metallothionein enhancer and promoter regions and transcription factors AP-1, NF-κB, and NF-AT were analyzed by chloramphenicol acetyltransferase (CAT) and electrophoretic mobility shift assays,... (More)

Exposure of cells to adverse environmental conditions invokes a genetically programmed series of events resulting in the induction of specific genes. The fluoroquinolone antibiotic ciprofloxacin has recently been reported to upregulate interleukin-2 (IL-2) gene induction. In the present investigation, the effect of ciprofloxacin at supratherapeutic concentrations on immediate-early (<2 h) gene expression in primary human peripheral blood lymphocytes was studied with Northern blots. In addition, transcriptional activity of IL-2 and metallothionein enhancer and promoter regions and transcription factors AP-1, NF-κB, and NF-AT were analyzed by chloramphenicol acetyltransferase (CAT) and electrophoretic mobility shift assays, respectively. The concentration of c-fos, c-jun, c-myc, junB, and fra-1 mRNAs was increased in activated peripheral blood lymphocytes incubated with ciprofloxacin compared to that in untreated controls. Ciprofloxacin increased CAT activity in stimulated lymphocytes transfected with plasmids containing either the IL-2 or metallothionein enhancer. Furthermore, among the transcription factors tested, AP-1 activity was increased in stimulated purified T helper lymphocytes incubated with ciprofloxacin compared to drug- free controls. Taken together, ciprofloxacin increased the levels of immediate-early transcripts, enhanced IL-2 and metallothionein promoter induction, and upregulated AP-1 concentrations in primary lymphocytes, reflecting a program commonly observed in mammalian stress responses.

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organization
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Contribution to journal
publication status
published
subject
in
Antimicrobial Agents and Chemotherapy
volume
42
issue
8
pages
8 pages
publisher
American Society for Microbiology
external identifiers
  • scopus:0031903256
ISSN
0066-4804
DOI
10.1128/AAC.42.8.1923
language
English
LU publication?
yes
id
bcb8e099-857a-4615-b894-7c4223447979
date added to LUP
2019-06-07 15:24:16
date last changed
2019-08-16 14:10:36
@article{bcb8e099-857a-4615-b894-7c4223447979,
  abstract     = {<p>Exposure of cells to adverse environmental conditions invokes a genetically programmed series of events resulting in the induction of specific genes. The fluoroquinolone antibiotic ciprofloxacin has recently been reported to upregulate interleukin-2 (IL-2) gene induction. In the present investigation, the effect of ciprofloxacin at supratherapeutic concentrations on immediate-early (&lt;2 h) gene expression in primary human peripheral blood lymphocytes was studied with Northern blots. In addition, transcriptional activity of IL-2 and metallothionein enhancer and promoter regions and transcription factors AP-1, NF-κB, and NF-AT were analyzed by chloramphenicol acetyltransferase (CAT) and electrophoretic mobility shift assays, respectively. The concentration of c-fos, c-jun, c-myc, junB, and fra-1 mRNAs was increased in activated peripheral blood lymphocytes incubated with ciprofloxacin compared to that in untreated controls. Ciprofloxacin increased CAT activity in stimulated lymphocytes transfected with plasmids containing either the IL-2 or metallothionein enhancer. Furthermore, among the transcription factors tested, AP-1 activity was increased in stimulated purified T helper lymphocytes incubated with ciprofloxacin compared to drug- free controls. Taken together, ciprofloxacin increased the levels of immediate-early transcripts, enhanced IL-2 and metallothionein promoter induction, and upregulated AP-1 concentrations in primary lymphocytes, reflecting a program commonly observed in mammalian stress responses.</p>},
  author       = {Riesbeck, Kristian and Forsgren, Arne and Henriksson, Agnethe and Bredberg, Anders},
  issn         = {0066-4804},
  language     = {eng},
  month        = {08},
  number       = {8},
  pages        = {1923--1930},
  publisher    = {American Society for Microbiology},
  series       = {Antimicrobial Agents and Chemotherapy},
  title        = {Ciprofloxacin induces an immunomodulatory stress response in human T lymphocytes},
  url          = {http://dx.doi.org/10.1128/AAC.42.8.1923},
  volume       = {42},
  year         = {1998},
}