UVA activated 8-MOP and chlorpromazine inhibit release of TNF-alpha by post-transcriptional regulation.
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.
Wolnicka-Glubisz
Agnieszka
A
Department of Biophysics, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland.
Sarna
Tadeusz
T
Klosner
Gabriele
G
Knobler
Robert
R
Trautinger
Franz
F
D045744:Cell Line, Tumor; D002746:Chlorpromazine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008730:Methoxsalen / Q000494:pharmacology*; D010778:Photochemotherapy; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells; D014467:Ultraviolet Therapy
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002746:Chlorpromazine; D008730:Methoxsalen