Karrer, Sigrid and Bosserhoff, Anja Kathrin and Weiderer, Petra and Landthaler, Michael and Szeimies, Rolf-Markus (2003) Influence of 5-aminolevulinic acid and red light on collagen metabolism of human dermal fibroblasts. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 120 (2). pp. 325-331. ISSN 0022-202X
Full text not available from this repository. (Request a copy)Abstract
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 .
| Item Type: | Article |
|---|---|
| Uncontrolled 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 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Sep 2021 09:50 |
| Last Modified: | 20 Sep 2021 09:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39313 |
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