Ciprofloxacin induces an immunomodulatory stress response in human T lymphocytes
(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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- author
- Riesbeck, Kristian LU ; Forsgren, Arne LU ; Henriksson, Agnethe and Bredberg, Anders LU
- organization
- publishing date
- 1998-08-01
- type
- 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
-
- pmid:9687385
- 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
- 2024-09-03 23:53:27
@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 (<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}}, doi = {{10.1128/AAC.42.8.1923}}, volume = {{42}}, year = {{1998}}, }