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UVA activated 8-MOP and chlorpromazine inhibit release of TNF-alpha by post-transcriptional regulation.
- Source :
-
Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology [Photochem Photobiol Sci] 2004 Apr; Vol. 3 (4), pp. 334-6. Date of Electronic Publication: 2004 Feb 24. - Publication Year :
- 2004
-
Abstract
- There is evidence that regulation of inflammatory cytokines is among the immunomodulatory effects of photochemotherapy with 8-MOP and UVA. We have recently demonstrated that in the monocytoid cell line U937 incubation with 8-MOP and subsequent exposure to UVA is able to efficiently downregulate the release of TNF-alpha into the culture supernatant. Chlorpromazine, a well known photosensitising drug, was even more potent with regard to this effect. Based on these observations, in this study we further investigate the mechanisms of TNF-alpha inhibition by 8-MOP and CPZ photosensitization. For this purpose we determined intracellular protein levels and gene expression of TNF-alpha by western blot and quantitative real-time PCR, respectively. Our results indicate that the observed inhibition of TNF-alpha secretion after photochemotherapy is not due to downregulation of gene transcription but rather to a post-transcriptional mechanism. The observed decrease of intracellular TNF-alpha with CPZ and 8-MOP points to decreased protein synthesis or enhanced degradation. These findings demonstrate that posttranscriptional regulation of cytokine expression is a possible mechanism of action of photochemotherapy.
- Subjects :
- Cell Line, Tumor
Dose-Response Relationship, Drug
Gene Expression Regulation drug effects
Humans
RNA, Messenger genetics
Transcription, Genetic
Tumor Necrosis Factor-alpha antagonists & inhibitors
Tumor Necrosis Factor-alpha genetics
U937 Cells
Ultraviolet Therapy
Chlorpromazine pharmacology
Methoxsalen pharmacology
Photochemotherapy
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1474-905X
- Volume :
- 3
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology
- Publication Type :
- Academic Journal
- Accession number :
- 15052360
- Full Text :
- https://doi.org/10.1039/b302621c