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Tumor necrosis factor-α-accelerated degradation of type I collagen in human skin is associated with elevated matrix metalloproteinase (MMP)-1 and MMP-3 ex vivo.

Ågren MS, Schnabel R, Christensen LH, Mirastschijski U - Eur. J. Cell Biol. (2014)

Bottom Line: Levels of the collagenases MMP-8 and MMP-13 were insignificant and neither MMP-2 nor MMP-14 were associated with increased collagen degradation.Type I collagen formation was down-regulated in cultured compared with native skin explants but was not reduced further by TNF-α.TNF-α had no significant effect on epidermal apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Copenhagen Wound Healing Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark; Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: saag0005@regionh.dk.

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Apoptosis assessed by TUNEL immunohistofluorescence. (A) Digoxigenin-labeled 3′-OH DNA termini were detected by sheep polyclonal anti-digoxigenin antibody conjugated with fluorescein (red). Slides were mounted using medium containing 4′,6-diamidino-2-phenylindole (green). Representative sections of native (left), control-treated (middle) and TNF-α-treated (right) skin explants are shown. Epidermis is indicated by dashed line. Scale bars: 500 μm. (B) Total number of TUNEL-positive cells per epidermal area in mm2, determined in two sections from two explants from each donor by two blinded investigators by image analysis (NIS-Elements AR, Nikon), were used for the global calculations. Mean ± SEM (n = 4). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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fig0025: Apoptosis assessed by TUNEL immunohistofluorescence. (A) Digoxigenin-labeled 3′-OH DNA termini were detected by sheep polyclonal anti-digoxigenin antibody conjugated with fluorescein (red). Slides were mounted using medium containing 4′,6-diamidino-2-phenylindole (green). Representative sections of native (left), control-treated (middle) and TNF-α-treated (right) skin explants are shown. Epidermis is indicated by dashed line. Scale bars: 500 μm. (B) Total number of TUNEL-positive cells per epidermal area in mm2, determined in two sections from two explants from each donor by two blinded investigators by image analysis (NIS-Elements AR, Nikon), were used for the global calculations. Mean ± SEM (n = 4). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Mentions: Morphologically, no discernible dermal changes occurred with culturing of the skin explants for 8 days possibly with the exception of slightly decreased number of cells compared with native skin. Epidermis had partially separated from dermis with ensuing pyknosis in cultured as opposed to noncultured skin. The degree of epidermal detachment was extensive in the control (40–50% of the length) and TNF-α (30–40%) groups but suppressed with GM6001 (0–20%) treatment. Apoptosis, assessed by TUNEL immunofluorescence, was prominent in epidermis and sparse in dermis of cultured skin explants compared with native skin (Fig. 4A). There was no significant difference in epidermal apoptosis between the control and TNF-α groups (Fig. 4B).


Tumor necrosis factor-α-accelerated degradation of type I collagen in human skin is associated with elevated matrix metalloproteinase (MMP)-1 and MMP-3 ex vivo.

Ågren MS, Schnabel R, Christensen LH, Mirastschijski U - Eur. J. Cell Biol. (2014)

Apoptosis assessed by TUNEL immunohistofluorescence. (A) Digoxigenin-labeled 3′-OH DNA termini were detected by sheep polyclonal anti-digoxigenin antibody conjugated with fluorescein (red). Slides were mounted using medium containing 4′,6-diamidino-2-phenylindole (green). Representative sections of native (left), control-treated (middle) and TNF-α-treated (right) skin explants are shown. Epidermis is indicated by dashed line. Scale bars: 500 μm. (B) Total number of TUNEL-positive cells per epidermal area in mm2, determined in two sections from two explants from each donor by two blinded investigators by image analysis (NIS-Elements AR, Nikon), were used for the global calculations. Mean ± SEM (n = 4). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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Related In: Results  -  Collection

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fig0025: Apoptosis assessed by TUNEL immunohistofluorescence. (A) Digoxigenin-labeled 3′-OH DNA termini were detected by sheep polyclonal anti-digoxigenin antibody conjugated with fluorescein (red). Slides were mounted using medium containing 4′,6-diamidino-2-phenylindole (green). Representative sections of native (left), control-treated (middle) and TNF-α-treated (right) skin explants are shown. Epidermis is indicated by dashed line. Scale bars: 500 μm. (B) Total number of TUNEL-positive cells per epidermal area in mm2, determined in two sections from two explants from each donor by two blinded investigators by image analysis (NIS-Elements AR, Nikon), were used for the global calculations. Mean ± SEM (n = 4). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Mentions: Morphologically, no discernible dermal changes occurred with culturing of the skin explants for 8 days possibly with the exception of slightly decreased number of cells compared with native skin. Epidermis had partially separated from dermis with ensuing pyknosis in cultured as opposed to noncultured skin. The degree of epidermal detachment was extensive in the control (40–50% of the length) and TNF-α (30–40%) groups but suppressed with GM6001 (0–20%) treatment. Apoptosis, assessed by TUNEL immunofluorescence, was prominent in epidermis and sparse in dermis of cultured skin explants compared with native skin (Fig. 4A). There was no significant difference in epidermal apoptosis between the control and TNF-α groups (Fig. 4B).

Bottom Line: Levels of the collagenases MMP-8 and MMP-13 were insignificant and neither MMP-2 nor MMP-14 were associated with increased collagen degradation.Type I collagen formation was down-regulated in cultured compared with native skin explants but was not reduced further by TNF-α.TNF-α had no significant effect on epidermal apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Copenhagen Wound Healing Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark; Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: saag0005@regionh.dk.

Show MeSH
Related in: MedlinePlus