Photochemical & Photobiological Sciences Dynamic Article Links Cite this: Photochem. Photobiol. Sci., 2012, 11, 216 www.rsc.org/pps PAPER Human erythema and matrix metalloproteinase-1 mRNA induction, in vivo, share an action spectrum which suggests common chromophores† Angela Tewari,‡ a Christine Lahmann,‡§ b Robert Sarkany, a J¨ org Bergemann¶ b and Antony R. Young a Received 5th August 2011, Accepted 23rd September 2011 DOI: 10.1039/c1pp05243h Matrix metalloproteinase 1 (MMP-1) is widely regarded as a biomarker of photoageing. We tested the hypothesis that MMP-1 mRNA expression and erythema share a common action spectrum by comparing the effects of erythemally equivalent doses of UVB, UVA1 and solar simulated radiation (SSR) on acute MMP-1 mRNA expression in whole human skin in vivo. Our results show comparable MMP-1 expression with all three spectra, which supports our hypothesis. The sharing of an action spectrum implies common chromophores, one of which is likely to be DNA. We have previously shown that all spectra that we used readily induce cyclobutane thymine dimers (T<>T) in human epidermis in vivo but we lack quantitative data on damage to dermal DNA. This is important because we do not know if dermal MMP-1 induction occurs via direct damage to the dermis, or indirectly via damage to the epidermis. Our results show that UVB induces about 3 times more T<>T compared with erythemally equivalent doses of UVA1, which is similar to our published epidermal data. This supports previously published work that also implicates an unknown UVA1 chromophore for erythema and MMP-1 induction. However, the distribution of the dermal DNA damage varies considerably with spectrum. In the case of UVB it is primarily in the upper dermis, but with UVA1 it is evenly distributed. Thus, irrespective of chromophores, MMP-1 induction by direct dermal damage by both spectra is possible. The practical conclusions of our data are that the small (<5%) UVB content of solar UVR is likely to be the main cause of photoageing, at least in terms of MMP-1 expression. Furthermore, prevention of erythema by sunscreen use is likely to result in reduced MMP-1 expression. Introduction Photoageing and skin cancer are the normal long term conse- quences of exposure to solar ultraviolet radiation (UVR: ~295– 400 nm), especially in sun sensitive skin types I and II. Skin cancer is a major health problem and has been subject to extensive epidemiological and basic research. There has been relatively limited research into photoageing, even though this is often associated with skin cancer, and mouse studies have shown that neutrophil elastase deficient hairless mice are resistant to photoageing and UVR-induced squamous cell carcinoma (SCC), suggesting a mechanistic link. 1 The vast majority (>95%) of solar UVR is UVA (320–400 nm), of which UVA1 (340–400 nm) is the major (~75%) component, but action spectroscopy has shown that the much smaller (<5%) a King’s College London (KCL), King’s College London School of Medicine, Division of Genetics and Molecular Medicine, St John’s Institute of Dermatology, London, UK. E-mail: antony.r.young@kcl.ac.uk b Beiersdorf AG, Paul Gerson Unna Skin Research Centre, Hamburg, Germany †Contribution to the themed issue on the biology of UVA. ‡ Equal first authors. § PhD student with Beiersdorf when work was done. ¶ Current address: Department of Biomedical Engineering, Albstadt- Sigmaringen University of Applied Sciences, Sigmaringen, Germany. UVB (~295–320 nm) component is responsible for the majority of DNA photodamage (thymine dimers; T<>T) in human skin in vivo and sunburn; 2 this has led to the conclusion that DNA is an important chromophore for erythema. It is also widely accepted that UVB is the main cause of skin cancer, 3 though some have advocated an important role for UVA, especially for malignant melanoma. 4,5 UVA1 is increasingly used in high dose phototherapy for skin disorders 6 and is typically the major spectral component of tanning devices. 7 Most research on the effects of UVR on skin in vivo has focused on the epidermis because it is the target tissue for photocarcinogenesis. The dermis is also an important target, especially in the context of inflammation and photoageing. 8 The structural integrity and function of the dermis are dependent on its extracellular matrix (ECM), which is mainly composed of type I and type II collagen. 9 Collagen turnover is mediated by matrix metalloproteinases (MMP) 10 and their inhibitors (TIMP). MMP-1 is highly induced by UVR in resident keratinocytes and fibroblasts, as well as MMP-3 and MMP-9 in vivo. 10–12 Photoageing is thought to be caused by UVR-induced hydrolysis of the dermal ECM that is initiated by MMP-1; a blocking antibody to MMP-1 removed 95 ± 4% of collagenolytic activity from UVR-exposed human skin, strongly implicating MMP-1 as a major enzyme responsible for collagen degradation in photoageing. 13 216 | Photochem. Photobiol. Sci., 2012, 11, 216–223 This journal is © The Royal Society of Chemistry and Owner Societies 2012