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Toll-like receptor 3 activation is required for normal skin barrier repair following UV damage.

Borkowski AW, Kuo IH, Bernard JJ, Yoshida T, Williams MR, Hung NJ, Yu BD, Beck LA, Gallo RL - J. Invest. Dermatol. (2014)

Bottom Line: UV damage to the skin leads to the release of noncoding RNA (ncRNA) from necrotic keratinocytes that activates Toll-like receptor 3 (TLR3).This release of ncRNA triggers inflammation in the skin following UV damage.Combined, these data further validate the conclusion that recognition of endogenous RNA by TLR3 is an important step in the program of skin barrier repair.

View Article: PubMed Central - PubMed

Affiliation: Division of Dermatology, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

ABSTRACT
UV damage to the skin leads to the release of noncoding RNA (ncRNA) from necrotic keratinocytes that activates Toll-like receptor 3 (TLR3). This release of ncRNA triggers inflammation in the skin following UV damage. Recently, TLR3 activation was also shown to aid wound repair and increase the expression of genes associated with permeability barrier repair. Here, we sought to test whether skin barrier repair after UVB damage is dependent on the activation of TLR3. We observed that multiple ncRNAs induced expression of skin barrier repair genes, that the TLR3 ligand Poly (I:C) also induced expression and function of tight junctions, and that the ncRNA U1 acts in a TLR3-dependent manner to induce expression of skin barrier repair genes. These observations were shown to have functional relevance as Tlr3-/- mice displayed a delay in skin barrier repair following UVB damage. Combined, these data further validate the conclusion that recognition of endogenous RNA by TLR3 is an important step in the program of skin barrier repair.

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UVB-damaged keratinocyte products stimulate genes important for skinbarrierNormal human keratinocytes were treated with either 1 μg/ml Poly (I:C), sonicated keratinocytes, or UVB-treated keratinocytes for 24 hours. Real-time PCR was used to quantify mRNA levels and fold change values are calculated relative and normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression for (a) lipid transport (ABCA12), lipid metabolism (GBA and SMPD1), transglutaminase-1 (TGM1) and (b) desmosome (CDSN) and tight junction (OCLN,TJP1, and CLDN1) transcripts. Data are mean +/− SEM, n = 3, and are representative of at least three independent experiments. * = P < 0.05, ** = P < 0.01, *** = P < 0.001 compared to control. τ = P < 0.05, τ τ = P < 0.01, τ τ τ = P < 0.001 comparing sonicated to UVB treated NHEK treatments. One-way ANOVA with Bonferroni post test.
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Figure 1: UVB-damaged keratinocyte products stimulate genes important for skinbarrierNormal human keratinocytes were treated with either 1 μg/ml Poly (I:C), sonicated keratinocytes, or UVB-treated keratinocytes for 24 hours. Real-time PCR was used to quantify mRNA levels and fold change values are calculated relative and normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression for (a) lipid transport (ABCA12), lipid metabolism (GBA and SMPD1), transglutaminase-1 (TGM1) and (b) desmosome (CDSN) and tight junction (OCLN,TJP1, and CLDN1) transcripts. Data are mean +/− SEM, n = 3, and are representative of at least three independent experiments. * = P < 0.05, ** = P < 0.01, *** = P < 0.001 compared to control. τ = P < 0.05, τ τ = P < 0.01, τ τ τ = P < 0.001 comparing sonicated to UVB treated NHEK treatments. One-way ANOVA with Bonferroni post test.

Mentions: To detect whether products of UVB-damaged keratinocytes trigger expression of genes involved in skin barrier repair, we exposed cultured normal human epidermal keratinocytes (NHEK) to 15 mJ/cm2 UVB and then transferred these irradiated cells to nonirradiated NHEK cultures. The exposure of NHEK to the products of UVB-damaged keratinocytes caused significant increases in mRNA abundance of ATP-binding cassette sub-family A member 12 (ABCA12), glucocerebrosidase (GBA), acid sphingomyelinase (SMPD1), and transglutaminase 1 (TGM1) (Figure 1a).


Toll-like receptor 3 activation is required for normal skin barrier repair following UV damage.

Borkowski AW, Kuo IH, Bernard JJ, Yoshida T, Williams MR, Hung NJ, Yu BD, Beck LA, Gallo RL - J. Invest. Dermatol. (2014)

UVB-damaged keratinocyte products stimulate genes important for skinbarrierNormal human keratinocytes were treated with either 1 μg/ml Poly (I:C), sonicated keratinocytes, or UVB-treated keratinocytes for 24 hours. Real-time PCR was used to quantify mRNA levels and fold change values are calculated relative and normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression for (a) lipid transport (ABCA12), lipid metabolism (GBA and SMPD1), transglutaminase-1 (TGM1) and (b) desmosome (CDSN) and tight junction (OCLN,TJP1, and CLDN1) transcripts. Data are mean +/− SEM, n = 3, and are representative of at least three independent experiments. * = P < 0.05, ** = P < 0.01, *** = P < 0.001 compared to control. τ = P < 0.05, τ τ = P < 0.01, τ τ τ = P < 0.001 comparing sonicated to UVB treated NHEK treatments. One-way ANOVA with Bonferroni post test.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4289479&req=5

Figure 1: UVB-damaged keratinocyte products stimulate genes important for skinbarrierNormal human keratinocytes were treated with either 1 μg/ml Poly (I:C), sonicated keratinocytes, or UVB-treated keratinocytes for 24 hours. Real-time PCR was used to quantify mRNA levels and fold change values are calculated relative and normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression for (a) lipid transport (ABCA12), lipid metabolism (GBA and SMPD1), transglutaminase-1 (TGM1) and (b) desmosome (CDSN) and tight junction (OCLN,TJP1, and CLDN1) transcripts. Data are mean +/− SEM, n = 3, and are representative of at least three independent experiments. * = P < 0.05, ** = P < 0.01, *** = P < 0.001 compared to control. τ = P < 0.05, τ τ = P < 0.01, τ τ τ = P < 0.001 comparing sonicated to UVB treated NHEK treatments. One-way ANOVA with Bonferroni post test.
Mentions: To detect whether products of UVB-damaged keratinocytes trigger expression of genes involved in skin barrier repair, we exposed cultured normal human epidermal keratinocytes (NHEK) to 15 mJ/cm2 UVB and then transferred these irradiated cells to nonirradiated NHEK cultures. The exposure of NHEK to the products of UVB-damaged keratinocytes caused significant increases in mRNA abundance of ATP-binding cassette sub-family A member 12 (ABCA12), glucocerebrosidase (GBA), acid sphingomyelinase (SMPD1), and transglutaminase 1 (TGM1) (Figure 1a).

Bottom Line: UV damage to the skin leads to the release of noncoding RNA (ncRNA) from necrotic keratinocytes that activates Toll-like receptor 3 (TLR3).This release of ncRNA triggers inflammation in the skin following UV damage.Combined, these data further validate the conclusion that recognition of endogenous RNA by TLR3 is an important step in the program of skin barrier repair.

View Article: PubMed Central - PubMed

Affiliation: Division of Dermatology, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

ABSTRACT
UV damage to the skin leads to the release of noncoding RNA (ncRNA) from necrotic keratinocytes that activates Toll-like receptor 3 (TLR3). This release of ncRNA triggers inflammation in the skin following UV damage. Recently, TLR3 activation was also shown to aid wound repair and increase the expression of genes associated with permeability barrier repair. Here, we sought to test whether skin barrier repair after UVB damage is dependent on the activation of TLR3. We observed that multiple ncRNAs induced expression of skin barrier repair genes, that the TLR3 ligand Poly (I:C) also induced expression and function of tight junctions, and that the ncRNA U1 acts in a TLR3-dependent manner to induce expression of skin barrier repair genes. These observations were shown to have functional relevance as Tlr3-/- mice displayed a delay in skin barrier repair following UVB damage. Combined, these data further validate the conclusion that recognition of endogenous RNA by TLR3 is an important step in the program of skin barrier repair.

Show MeSH
Related in: MedlinePlus