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TSLP is differentially regulated by vitamin D3 and cytokines in human skin.

Landheer J, Giovannone B, Sadekova S, Tjabringa S, Hofstra C, Dechering K, Bruijnzeel-Koomen C, Chang C, Ying Y, de Waal Malefyt R, Hijnen D, Knol E - Immun Inflamm Dis (2015)

Bottom Line: The objective is to investigate the effect of VD3 (calcitriol) or calcipotriol on TSLP expression in normal human skin and skin from AD patients.The biological activity of calci(po)triol in human skin samples was demonstrated by the increased expression of the VD3-responsive Cyp24a1 gene.TSLP expression was induced by cytokines (IL-4, IL-13, and TNF-α) in skin samples from all three species.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology & Allergology, University Medical Center Utrecht Utrecht, the Netherlands.

ABSTRACT
Thymic stromal lymphopoietin (TSLP) plays an important role in allergic diseases and is highly expressed in keratinocytes in human lesional atopic dermatitis (AD) skin. In nonlesional AD skin TSLP expression can be induced by applying house dust mite allergen onto the skin in the atopy patch test. Several studies have demonstrated that the induction of TSLP expression in mouse skin does not only lead to AD-like inflammation of the skin, but also predisposes to severe inflammation of the airways. In mice, TSLP expression can be induced by application of the 1,25-dihydroxyvitamin D3 (VD3) analogue calcipotriol and results in the development of eczema-like lesions. The objective is to investigate the effect of VD3 (calcitriol) or calcipotriol on TSLP expression in normal human skin and skin from AD patients. Using multiple ex vivo experimental setups, the effects of calci(po)triol on TSLP expression by normal human skin, and skin from AD patients were investigated and compared to effects of calcipotriol on mouse and non-human primates (NHP) skin. No induction of TSLP expression (mRNA or protein) was observed in human keratinocytes, normal human skin, nonlesional AD skin, or NHP skin samples after stimulation with calcipotriol or topical application of calcitriol. The biological activity of calci(po)triol in human skin samples was demonstrated by the increased expression of the VD3-responsive Cyp24a1 gene. TSLP expression was induced by cytokines (IL-4, IL-13, and TNF-α) in skin samples from all three species. In contrast to the findings in human and NHP, a consistent increase in TSLP expression was confirmed in mouse skin biopsies after stimulation with calcipotriol. VD3 failed to induce expression of TSLP in human or monkey skin in contrast to mouse, implicating careful extrapolation of this often-used mouse model to AD patients.

No MeSH data available.


Related in: MedlinePlus

Effects of calcipotriol on TSLP expression in normal human skin biopsies at 24 and 48 h of treatment. (a) TSLP mRNA expression; (b) TSLP protein expression; (c) Cyp24 gene expression. Data are representative of three independent skin donors and are shown as mean ± SEM.; *P < 0.05.
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fig02: Effects of calcipotriol on TSLP expression in normal human skin biopsies at 24 and 48 h of treatment. (a) TSLP mRNA expression; (b) TSLP protein expression; (c) Cyp24 gene expression. Data are representative of three independent skin donors and are shown as mean ± SEM.; *P < 0.05.

Mentions: The results above demonstrated that isolated primary human keratinocytes do not show induction of TSLP expression in response to VD3. However, dermal fibroblasts, mast cells and basophils are also able to produce TSLP in skin 4,12. Therefore, it was important to study TSLP expression in calcipotriol-stimulated intact normal human skin biopsies, which retain all the different cell types and structures present in human skin. When punch biopsies were cultured submerged for 24 or 48 h in calcipotriol (100 nM)-containing medium, no increase in TSLP mRNA (Fig. 2a) or protein (Fig. 2b) levels was observed. However, the IL-4, IL-13, and TNF-α combination was able to induce TSLP gene expression and protein release (Fig. 2a, b). Increased Cyp24a1 expression confirmed the biological activity of calcipotriol (Fig. 2c).


TSLP is differentially regulated by vitamin D3 and cytokines in human skin.

Landheer J, Giovannone B, Sadekova S, Tjabringa S, Hofstra C, Dechering K, Bruijnzeel-Koomen C, Chang C, Ying Y, de Waal Malefyt R, Hijnen D, Knol E - Immun Inflamm Dis (2015)

Effects of calcipotriol on TSLP expression in normal human skin biopsies at 24 and 48 h of treatment. (a) TSLP mRNA expression; (b) TSLP protein expression; (c) Cyp24 gene expression. Data are representative of three independent skin donors and are shown as mean ± SEM.; *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4386913&req=5

fig02: Effects of calcipotriol on TSLP expression in normal human skin biopsies at 24 and 48 h of treatment. (a) TSLP mRNA expression; (b) TSLP protein expression; (c) Cyp24 gene expression. Data are representative of three independent skin donors and are shown as mean ± SEM.; *P < 0.05.
Mentions: The results above demonstrated that isolated primary human keratinocytes do not show induction of TSLP expression in response to VD3. However, dermal fibroblasts, mast cells and basophils are also able to produce TSLP in skin 4,12. Therefore, it was important to study TSLP expression in calcipotriol-stimulated intact normal human skin biopsies, which retain all the different cell types and structures present in human skin. When punch biopsies were cultured submerged for 24 or 48 h in calcipotriol (100 nM)-containing medium, no increase in TSLP mRNA (Fig. 2a) or protein (Fig. 2b) levels was observed. However, the IL-4, IL-13, and TNF-α combination was able to induce TSLP gene expression and protein release (Fig. 2a, b). Increased Cyp24a1 expression confirmed the biological activity of calcipotriol (Fig. 2c).

Bottom Line: The objective is to investigate the effect of VD3 (calcitriol) or calcipotriol on TSLP expression in normal human skin and skin from AD patients.The biological activity of calci(po)triol in human skin samples was demonstrated by the increased expression of the VD3-responsive Cyp24a1 gene.TSLP expression was induced by cytokines (IL-4, IL-13, and TNF-α) in skin samples from all three species.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology & Allergology, University Medical Center Utrecht Utrecht, the Netherlands.

ABSTRACT
Thymic stromal lymphopoietin (TSLP) plays an important role in allergic diseases and is highly expressed in keratinocytes in human lesional atopic dermatitis (AD) skin. In nonlesional AD skin TSLP expression can be induced by applying house dust mite allergen onto the skin in the atopy patch test. Several studies have demonstrated that the induction of TSLP expression in mouse skin does not only lead to AD-like inflammation of the skin, but also predisposes to severe inflammation of the airways. In mice, TSLP expression can be induced by application of the 1,25-dihydroxyvitamin D3 (VD3) analogue calcipotriol and results in the development of eczema-like lesions. The objective is to investigate the effect of VD3 (calcitriol) or calcipotriol on TSLP expression in normal human skin and skin from AD patients. Using multiple ex vivo experimental setups, the effects of calci(po)triol on TSLP expression by normal human skin, and skin from AD patients were investigated and compared to effects of calcipotriol on mouse and non-human primates (NHP) skin. No induction of TSLP expression (mRNA or protein) was observed in human keratinocytes, normal human skin, nonlesional AD skin, or NHP skin samples after stimulation with calcipotriol or topical application of calcitriol. The biological activity of calci(po)triol in human skin samples was demonstrated by the increased expression of the VD3-responsive Cyp24a1 gene. TSLP expression was induced by cytokines (IL-4, IL-13, and TNF-α) in skin samples from all three species. In contrast to the findings in human and NHP, a consistent increase in TSLP expression was confirmed in mouse skin biopsies after stimulation with calcipotriol. VD3 failed to induce expression of TSLP in human or monkey skin in contrast to mouse, implicating careful extrapolation of this often-used mouse model to AD patients.

No MeSH data available.


Related in: MedlinePlus