UVB Upregulates the Antimicrobial Protein hCAP18 mRNA in Human Skin

Mallbris, Lotus; Edström, Desirée Wiegleb; Sundblad, Lisa; Granath, Fredrik; Ståhle, Mona

doi:10.1111/j.0022-202x.2005.23872.x

Cited by 59 publications

(53 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, 1,25D3 was found to induce human CAMP expression in keratinocytes in vitro and in vivo (6)(7)(8), and an observed increase in cathelicidin expression after UVB irradiation was proposed to be caused by an increase in 1,25D3 (30). These observations led us to examine whether the regulation of vitamin D 3 is involved in the wound repair response.…”

Section: Figurementioning

confidence: 97%

Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D–dependent mechanism

Schauber¹,

Dorschner²,

Coda³

et al. 2007

J. Clin. Invest.

598

541

View full text Add to dashboard Cite

An essential element of the innate immune response to injury is the capacity to recognize microbial invasion and stimulate production of antimicrobial peptides. We investigated how this process is controlled in the epidermis. Keratinocytes surrounding a wound increased expression of the genes coding for the microbial pattern recognition receptors CD14 and TLR2, complementing an increase in cathelicidin antimicrobial peptide expression. These genes were induced by 1,25(OH) 2 vitamin D 3 (1,25D3; its active form), suggesting a role for vitamin D 3 in this process. How 1,25D3 could participate in the injury response was explained by findings that the levels of CYP27B1, which converts 25OH vitamin D 3 (25D3) to active 1,25D3, were increased in wounds and induced in keratinocytes in response to TGF-β 1 . Blocking the vitamin D receptor, inhibiting CYP27B1, or limiting 25D3 availability prevented TGF-β 1 from inducing cathelicidin, CD14, or TLR2 in human keratinocytes, while CYP27B1-deficient mice failed to increase CD14 expression following wounding. The functional consequence of these observations was confirmed by demonstrating that 1,25D3 enabled keratinocytes to recognize microbial components through TLR2 and respond by cathelicidin production. Thus, we demonstrate what we believe to be a previously unexpected role for vitamin D 3 in innate immunity, enabling keratinocytes to recognize and respond to microbes and to protect wounds against infection.

show abstract

Section: Figurementioning

confidence: 97%

Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D–dependent mechanism

Schauber¹,

Dorschner²,

Coda³

et al. 2007

J. Clin. Invest.

598

541

View full text Add to dashboard Cite

show abstract

“…This control by VDR is underscored by studies showing that vdr -/ -mice are more sensitive to chemicals that induce inflammation than their wild-types counterparts (135) . The normally protective effect of inflammation that occurs under other conditions is lost through this VDR-mediated suppression but is compensated by the induction of a cohort of antimicrobial and antifungal genes via the innate immune response (136)(137)(138) . The induction of antimicrobials not only prevents infection in damaged tissue but can be cytotoxic for cells with increased levels of anion phospholipids within their membranes, a common feature of transformed cells (139) ; experimental results are, however, conflicting.…”

Section: The Vitamin D Receptor In Dna Damage and Repairmentioning

confidence: 99%

The vitamin D receptor in cancer

2008

View full text Add to dashboard Cite

Over the last 25 years roles have been established for vitamin D receptor (VDR) in influencing cell proliferation and differentiation. For example, murine knock-out approaches have revealed a role for the VDR in controlling mammary gland growth and function. These actions appear widespread, as the enzymes responsible for 1a,25-dihydroxycholecalciferol generation and degradation, and the VDR itself, are all functionally present in a wide range of epithelial and haematopoietic cell types. These findings, combined with epidemiological and functional data, support the concept that local, autocrine and paracrine VDR signalling exerts control over cell-fate decisions in multiple cell types. Furthermore, the recent identification of bile acid lithocholic acid as a VDR ligand underscores the environmental sensing role for the VDR. In vitro and in vivo dissection of VDR signalling in cancers (e.g. breast, prostate and colon) supports a role for targeting the VDR in either chemoprevention or chemotherapy settings. As with other potential therapeutics, it has become clear that cancer cells display de novo and acquired genetic and epigenetic mechanisms of resistance to these actions. Consequently, a range of experimental and clinical options are being developed to bring about more targeted actions, overcome resistance and enhance the efficacy of VDR-centred therapeutics. The cancer burdenThe impact of cancer continues to be one of the greatest burdens in the developed world and is also increasingly impacting on the developing world. Approximately 1 . 5 million individuals will die from breast, colon or prostate cancer this year, and the total number of deaths from cancer accounts for 13 % of all deaths worldwide and for one in every four deaths in the UK and USA (1) . The impact is also economic; $280 · 10 9 is spent annually worldwide on the treatment of patients. Many cancers are however preventable, and through lifestyle choices such as smoking, diet and exercise the worldwide incidence of cancer could be cut by 40 % (2,3) . Major risk factors for cancer DietRecently, the appreciation of the impact of diet on cancer has come to the fore, with a number of studies establishing unequivocal relationships between diet and cancer initiation and progression. Reflecting the accumulation of these data, the WHO has now stated that diet forms the secondmost preventable cause of cancer (after smoking) (3) . This impact will rise further as a result of demographic factors, and quite possibly because of changing dietary habits worldwide, which will contribute further to the projected increase in cancer incidence in developing nations. Highprofile malignancies such as breast, prostate, and colon cancer typify this scenario, in which the aetiology of the disease reflects the cumulative impact of dietary factors over an individual's lifetime (4)(5)(6) . The relationship between diet and disease is already exploited clinically, e.g. in the Selenium and Vitamin E Cancer Prevention Trial to assess the chemoprevention potential of vitamin E ...

show abstract

“…Moreover, UVB irradiation led to elevated cutaneous cathelicidin mRNA expression in vivo parallelled by an increase in VDR mRNA [23]. UVB-dependent production of 1,25(OH) 2 D 3 in the skin with subsequent induction of cathelicidin (fig.…”

Section: Vitamin D and Innate Immunity: Of Light And Infection – Finsmentioning

confidence: 99%

The Epidermal Vitamin D System and Innate Immunity: Some More Light Shed on This Unique Photoendocrine System?

Segaert

Simonart

2008

Dermatology

View full text Add to dashboard Cite

UVB Upregulates the Antimicrobial Protein hCAP18 mRNA in Human Skin

Cited by 59 publications

References 10 publications

Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D–dependent mechanism

Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D–dependent mechanism

The vitamin D receptor in cancer

The Epidermal Vitamin D System and Innate Immunity: Some More Light Shed on This Unique Photoendocrine System?

Contact Info

Product

Resources

About