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| PHOTODYNAMIC THERAPY INDUCES EXPRESSION OF INTERLEUKIN-6 BY ACTIVATION OF AP-1 BUT NOT NF-KAPPA-B DNA-BINDING |
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| Author(s): KICK G, MESSER G, GOETZ A, PLEWIG G, KIND P |
| Source: CANCER RESEARCH Volume: 55 Issue: 11 Pages: 2373-2379 Published: JUN 1 1995 |
| Times Cited: 63 References: 52 |
| Abstract: Inducibility and regulation of the pleiotropic cytokine interleukin 6 (IL-6) upon photodynamic therapy (PDT) was studied in the epithelial cell line HeLa. Photofrin-mediated photosensitization resulted in a rapid and dose-dependent induction of IL-6 mRNA production. Maximal levels were reached after 4 h and had decreased to baseline levels after 24 h. This photochemical induction of IL-6 transcription was followed by a strong secretion of IL-6 protein. In comparison to stimulation by 12-O-tetradecanoylphorbol-13-acetate, the kinetics of IL-6 mRNA and protein synthesis after PDT were delayed, although the maximal amounts of secreted IL-6 protein were comparable. As compared to UV irradiation, on the other hand, PDT-induced IL-6 protein levels were 2- to 10-fold higher and were detectable 4 h earlier. Several potentially relevant regulatory DNA elements of the IL-6 promoter were analyzed by gel retardation assays for PDT-induced protein binding. Interestingly, increased AP-1 DNA binding was detected only at the distal AP-1-specific motif and not at the proximal site, differing in 1 bp. Binding of c-Fos-containing AP-1 heterodimers to the specific motif was up-regulated 30 min after PDT, reaching maximal activity at 4 h. This PDT-induced AP-1 activation was independent from protein kinase C activity. Photosensitization did not induce increased binding at the well-characterized NF-kappa B element, nor at the multiple cytokine- and second messenger-responsive element of the IL-6 promoter. By analyzing the molecular mechanisms of IL-6 up-regulation upon PDT, we provide evidence for regulatory differences compared to UV light, ionizing irradiation, or stimulation by phorbol ester. Furthermore, this study suggests that the ''proinflammatory'' cytokine IL-6 might be involved in the inflammatory reaction and subsequent immunological antitumor responses. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV MUNICH, DEPT DERMATOL, DERMATOL KLIN, D-80337 MUNICH, GERMANY
2. UNIV MUNICH, INST ANESTHESIOL, D-80337 MUNICH, GERMANY |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: RA145 |
| ISSN: 0008-5472 |
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