Hong SP, Kim MJ, Jung MY et al.Biopositive effects of low-dose UVB on epidermis: coordinate upregulation of antimicrobial peptides and permeability barrier reinforcement. J Invest Dermatol Symp Proc 128:2880-2887

Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea.
Journal of Investigative Dermatology (Impact Factor: 6.37). 07/2008; 128(12):2880-7. DOI: 10.1038/jid.2008.169
Source: PubMed

ABSTRACT Whereas high-dose ultraviolet B (UVB) is detrimental to the epidermal permeability barrier, suberythemal doses of UVB are used to treat atopic dermatitis (AD), which is characterized by defective permeability barrier and antimicrobial function. As epidermal permeability barrier and antimicrobial peptide (AMP) expression are coregulated and interdependent functions, we hypothesized that suberythemal doses of UVB exposure could regulate AMP expression in parallel with permeability barrier function. Hairless mice were exposed to 40 mJ cm(-2) UVB (about 1/2 minimal erythema dose) daily for 1 or 3 days. Twenty-four hours after the last exposure, epidermal barrier function was assessed and skin specimens were taken for western blotting, immunohistochemistry, and quantitative reverse transcription-PCR for mouse beta-defensin (mBD)-2, mBD3 and cathelin-related antimicrobial peptide (CRAMP). mRNA levels of the vitamin D receptor (VDR), 1alpha-hydroxylase and key epidermal lipid synthetic enzymes were also quantified. After 3 days of UVB exposure, acceleration of barrier recovery and augmentation in expression of epidermal differentiation markers (for example, involucrin and filaggrin) occurred in parallel with increased mBD2, mBD3, and CRAMP expression at both the mRNA and protein level. VDR, 1alpha-hydroxylase, and the major epidermal lipid synthetic enzymes were also upregulated. When an inhibitor of 1alpha, 25 dihydroxyvitamin D(3) formation, ketoconazole, was applied immediately after UVB exposure, the cutaneous vitamin D system was inhibited, which in turn blocked epidermal lipid synthesis, AMP expression, and permeability barrier homeostasis, suggesting that the beneficial effect of low-dose UVB depends, at least in part, on activation of the cutaneous vitamin D system. Our results provide new insights into the mechanisms whereby low-dose UVB comprises effective therapy for AD.

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    • "In addition, Hong et al. (2008) have shown increased mouse b-defensin 2 and 3 expression at both the mRNA and protein level after 3 days of UVB exposure in parallel with a beneficial effect on permeability barrier function, which depends, at least in part, on activation of the cutaneous vitamin D system. "
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    ABSTRACT: Atopic dermatitis (AD) is a common chronic inflammatory skin disease that has increased in prevalence over the last several decades in industrialized countries. AD is a multifactorial, heterogenous disease with a variety of defects in the immune system, in antimicrobial defense mechanisms and epidermal barrier integrity, which collectively contribute to the risk and severity of AD development. Vitamin D receptor (VDR) signaling has been shown to be important not only in the immune system but also in the skin and in particular keratinocytes to regulate skin homeostasis and epidermal barrier function. However, this work aimed to analyze the role and clinical efficiency of VDR activation by a VDR agonist without calcium-mobilizing activity in a mouse model of allergen-triggered eczema. We show that the systemic administration of the low-calcemic VDR agonist significantly improved the allergen-triggered eczema. Thereby, forkhead box P3 (Foxp3)-expressing regulatory T cells, revealed to have a role in AD, were selectively increased in the skin of VDR agonist-treated mice. Moreover, our results demonstrate a marked induction of skin barrier gene and antimicrobial peptide gene expression in skin lesions of VDR agonist-treated mice. Thus, our study provides evidence that systemic VDR agonist treatment may improve allergen-triggered eczema in vivo.
    Journal of Investigative Dermatology 09/2011; 132(2):330-6. DOI:10.1038/jid.2011.296 · 6.37 Impact Factor
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    • "Mallbris et al. (2005) showed that 1 MED UVB significantly upregulated VDR mRNA expression at 24–28 hours in healthy normal skin. Hong et al. (2008) showed that 0.5 MED UVB for three consecutive days significantly increased mRNA VDR expression in hairless mice. Our irradiation protocol demonstrates that the effects of an acute highly erythemal UVB dose are abrogated by previous exposure to daily suberythemal UVB for at least 10 days. "
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    ABSTRACT: IVD, integrated density value; MED, minimal erythema dose; VDR, vitamin D receptor
    Journal of Investigative Dermatology 08/2011; 131(11):2332-5. DOI:10.1038/jid.2011.209 · 6.37 Impact Factor
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    • "Thus, these studies further support a close link between UV-B-induced changes in permeability barrier function and cathelicidin expression. Furthermore, together with the work of Hong, et al. on suberythemogenic UV-B (Hong, SP, et al., 2008), these studies have potential clinical implications about how UV-B irradiation should be deployed for the treatment of inflammatory dermatoses. While current recommendations propose 'pushing' UV-B phototherapy doses upwards into the erythemogenic range, this approach clearly could pose adverse consequences not only for both permeability barrier function, but also for cutaneous antimicrobial defense. "
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    ABSTRACT: Two critical defensive functions of the outer epidermis, the permeability barrier and antimicrobial defense, share certain structural and biochemical features. Moreover, three antimicrobial peptides (AMPs), i.e., mouse β-defensin 3 (mBD3), mouse cathelicidin antimicrobial peptide (mCAMP), and the neuroendocrine peptide, catestatin (Cst), all localize to the outer epidermis, and both mBD3 and mCAMP are secreted from the epidermal lamellar bodies with other organelle contents that subserve the permeability barrier. These three AMPs are upregulated in response to acute permeability barrier disruption, whereas conversely, mCAMP-/- mice (unable to combat Gram-positive pathogens) also display abnormal barrier homeostasis. To determine further whether these two functions are co-regulated, we investigated changes in immunostaining for these three AMPs in skin samples in which the permeability barrier function in mice had been either compromised or enhanced. Compromised or enhanced barrier function correlated with reduced or enhanced immunohistochemical expression of mCAMP, respectively, but conversely with Cst expression, likely due to the role of this AMP as an endogenous inhibitor of cathelicidin expression. mBD3 expression correlated with experimental barrier perturbations, but poorly with developmental changes in barrier function. These studies show that changes in cathelicidin and Cst expression parallel changes in permeability barrier status, with a less clear relationship with mBD3 expression.
    Journal of Investigative Dermatology 07/2011; 131(11):2263-70. DOI:10.1038/jid.2011.210 · 6.37 Impact Factor
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