| Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Journal of Investigative Dermatology | ||||
| Verlag: | BLACKWELL PUBLISHING INC | ||||
| Ort der Veröffentlichung: | MALDEN | ||||
| Band: | 120 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 2 | ||||
| Seitenbereich: | S. 325-331 | ||||
| Datum: | 2003 | ||||
| Institutionen: | Medizin > Lehrstuhl für Dermatologie und Venerologie Medizin > Lehrstuhl für Pathologie | ||||
| Identifikationsnummer: |
| ||||
| Stichwörter / Keywords: | TOPICAL PHOTODYNAMIC THERAPY; ENDOGENOUS PROTOPORPHYRIN-IX; DELTA-AMINOLEVULINIC-ACID; A-INDUCED SYNTHESIS; ULTRAVIOLET-A; LOCALIZED SCLERODERMA; SINGLET OXYGEN; MATRIX METALLOPROTEINASES; METHOXSALEN PSORALEN; RADIATION PUVA; collagen type I; collagen type III; extracellular matrix; immunomodulation; localized scleroderma; matrix metalloproteinase; photodynamic therapy; skin sclerosis; tissue inhibitor of metalloproteinase | ||||
| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 72434 |
Web of ScienceZusammenfassung
Patients with localized scleroderma receiving topical photodynamic therapy with 5-aminolevulinic acid show a reduction in skin tightness, suggesting that this therapy reduces skin sclerosis. To investigate potential mechanisms, the effects of 5-aminolevulinic acid and light on collagen metabolism were studied in vitro . Normal and scleroderma fibroblasts were treated with sublethal doses of ...
Zusammenfassung
Patients with localized scleroderma receiving topical photodynamic therapy with 5-aminolevulinic acid show a reduction in skin tightness, suggesting that this therapy reduces skin sclerosis. To investigate potential mechanisms, the effects of 5-aminolevulinic acid and light on collagen metabolism were studied in vitro . Normal and scleroderma fibroblasts were treated with sublethal doses of 5-aminolevulinic acid and red light and transferred to three-dimensional collagen lattices. Cell supernatants were taken 6-72 h after photodynamic therapy to determine protein levels of the matrix metalloproteinases 1, 2, and 3, and of their inhibitors, tissue inhibitor of metalloproteinase 1 and 2 by enzyme-linked immunosorbent assay. Cellular mRNA expression of these proteins and of collagen type I and III was measured by quantitative real-time polymerase chain reaction. A significant, time-dependent induction of matrix metalloproteinase 1 (up to 2.4-fold after 48 h) and matrix metalloproteinase 3 (up to 4.3-fold after 48 h) protein levels was seen after 5-aminolevulinic acid-photodynamic therapy. Irradiation with ultraviolet A light, used as a positive control, showed a similar induction of matrix metalloproteinase 1 (2.3-fold after 48 h). The mRNA levels of matrix metalloproteinase 1 and matrix metalloproteinase 3 were significantly increased 12 h after irradiation, whereas collagen type I mRNA was strongly decreased already 6 h following irradiation. Collagen type III, tissue inhibitor of metalloproteinase 1, and matrix metalloproteinase 2 did not change after photodynamic therapy. Addition of nontoxic concentrations of sodium azide, a singlet-oxygen quencher, significantly inhibited induction of matrix metalloproteinase 1 by 5-aminolevulinic acid and light. These data show that 5-aminolevulinic acid and light induce matrix metalloproteinase 1 and matrix metalloproteinase 3 expression in normal and scleroderma fibroblasts in a singlet oxygen-dependent way while reducing collagen type I mRNA expression. Induction of collagen-degrading enzymes together with reduction of collagen production might be responsible for the anti-sclerotic effects of 5-aminolevulinic acid-photodynamic therapy observed in vivo .
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