UVA activated 8-MOP and chlorpromazine inhibit release of TNF-alpha by post-transcriptional regulation.
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| 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.
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| Authors | Agnieszka Wolnicka-Glubisz, Tadeusz Sarna, Gabriele Klosner, Robert Knobler, Franz Trautinger |
| Journal | Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology (Photochem Photobiol Sci) Vol. 3 Issue 4 Pg. 334-6 (Apr 2004) ISSN: 1474-905X [Print] England |
| PMID | 15052360 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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