5 research outputs found
Transepidermal UV radiation of scalp skin ex vivo induces hair follicle damage that is alleviated by the topical treatment with caffeine
Objectives
Although the effect of ultraviolet radiation (UVR) on human skin has been extensively studied, very little is known on how UVR impacts on hair follicle (HF) homeostasis. Here, we investigated how solar spectrum UVR that hits the human skin surface impacts on HF biology, and whether any detrimental effects can be mitigated by a widely used cosmetic and nutraceutical ingredient, caffeine.
Methods
Human scalp skin with terminal HFs was irradiated transepidermally ex vivo using either 10 J/cm2 UVA (340â440 nm) + 20 mJ/cm2 UVB (290â320 nm) (low dose) or 50 J/cm2 UVA + 50 mJ/cm2 UVB (high dose) and organâcultured under serumâfree conditions for 1 or 3 days. 0.1% caffeine (5.15 mmol/L) was topically applied for 3 days prior to UV exposure with 40 J/cm2 UVA + 40 mJ/cm2 UVB and for 3 days after UVR. The effects on various toxicity and vitality readâout parameters were measured in defined skin and HF compartments.
Results
Consistent with previous results, transepidermal UVR exerted skin cytotoxicity and epidermal damage. Treatment with high and/or low UVA+UVB doses also induced oxidative DNA damage and cytotoxicity in human HFs. In addition, it decreased proliferation and promoted apoptosis of HF outer root sheath (ORS) and hair matrix (HM) keratinocytes, stimulated catagen development, differentially regulated the expression of HF growth factors, and induced perifollicular mast cell degranulation. UVRâmediated HF damage was more severe after irradiation with high UVR dose and reached also proximal HF compartments. The topical application of 0.1% caffeine did not induce skin or HF cytotoxicity and stimulated the expression of IGFâ1 in the proximal HF ORS. However, it promoted keratinocyte apoptosis in selected HF compartments. Moreover, caffeine provided protection towards UVRâmediated HF cytotoxicity and dystrophy, keratinocyte apoptosis, and tendential upâregulation of the catagenâpromoting growth factor.
Conclusion
Our study highlights the clinical relevance of our scalp UV irradiation ex vivo assay and provides the first evidence that transepidermal UV radiation negatively affects important human HF functions. This suggests that it is a sensible prophylactic strategy to integrate agents such as caffeine that can act as HF photoprotectants into sunâprotective cosmeceutical and nutraceutical formulations.
We show here that solar UVA+UVB radiation impacting on the skin surface negatively affects HF functions, namely it triggers HF cytotoxicity, dystrophy, oxidative DNA damage, decrease in keratinocyte proliferation and increase in their apoptosis, stimulation of the production of transforming growth factor (TGF)âÎČ2 and decrease in insulin growth factor (IGF)â1 expression in ORS keratinocytes, premature catagen development, and perifollicular mast cell degranulation. UVâmediated damage is present throughout the HF length, but is more prominent in the upper layers of the skin (distal HF), as compared to the lower HF (central and proximal). Our study also shows that the topical application of 0.1% caffeine protects HFs from UVRâmediated damaged, namely it alleviated UVâmediated HF cytotoxicity and dystrophy, keratinocyte apoptosis in the distal and central ORS, and increased expression of TGFâÎČ2 in the proximal ORS.
Résumé
Objectifs
Alors que l'effet de rayons ultraviolets (RUV) sur la peau humaine a Ă©tĂ© largement Ă©tudiĂ©, on sait trĂšs peu de choses de l'impact des UV sur l'homĂ©ostasie du follicule pileux (FP). Ici, nous avons Ă©tudiĂ© l'effet du spectre des RUV solaires qui atteignent la surface de la peau humaine sur la biologie du FP, et si tout effet nocif peut ĂȘtre attĂ©nuĂ© par de la cafĂ©ine, un ingrĂ©dient cosmĂ©tique et neutraceutique largement utilisĂ©.
MĂthodes
Une peau de cuir chevelu humain avec ses FP terminaux a Ă©tĂ© irradiĂ©e ex vivo via lâĂ©piderme soit par 10 J/cm2 dâUVA (340â440 nm) + 20 mJ/cm2 dâUVB (290â320 nm) (dose faible) soit par 50 J/cm2 dâUVA + 50 mJ/cm2 dâUVB (dose Ă©levĂ©e) et placĂ©e en culture sans sĂ©rum pendant 1 ou 3 jours. 0,1% (5,15 mM) de cafĂ©ine a Ă©tĂ© appliquĂ©e par voie topique pendant 3 jours avant l'exposition aux UV Ă raison de 40 J/cm2 dâUVA + 40 mJ/cm2 UVB et pendant 3 jours aprĂšs l'exposition aux RUV. Les effets sur divers paramĂštres de toxicitĂ© et de vitalitĂ© ont Ă©tĂ© mesurĂ©s au niveau de compartiments dĂ©finis de la peau et des FP.
RĂsultats
CohĂ©rent avec les rĂ©sultats prĂ©cĂ©dents, les RUV transĂ©pidermique ont exercĂ© une cytotoxicitĂ© au niveau de la peau et des lĂ©sions Ă©pidermiques. Le traitement par des doses Ă©levĂ©es et/ou faibles dâUVA+UVB a Ă©galement induit des lĂ©sions oxydatives de lâADN et une cytotoxicitĂ© au niveau des FP humains. En outre, il a diminuĂ© la prolifĂ©ration et favorisĂ© l'apoptose de la gaine externe de la racine (ORS) du FP et des kĂ©ratinocytes de la matrice des cheveux (MC), a stimulĂ© le dĂ©veloppement de la phase catagĂšne, a rĂ©gulĂ© de maniĂšre diffĂ©rentielle l'expression des facteurs de croissance des FP, et induit une dĂ©granulation pĂ©rifolliculaire des mastocytes. Les lĂ©sions du FP mĂ©diĂ©es par les RUV Ă©taient plus graves aprĂšs une irradiation par dose Ă©levĂ©e de RUV et atteignaient Ă©galement les compartiments proximaux du FP. L'application topique de 0,1 % de cafĂ©ine n'a pas induit de cytotoxicitĂ© de la peau ou du FP et a stimulĂ© l'expression dâIGFâ1 dans la partie proximale de lâORS du FP. Cependant, elle a promu l'apoptose des kĂ©ratinocytes dans certains compartiments de FP. En outre, la cafĂ©ine a fourni une protection des FP contre la cytotoxicitĂ© et la dystrophie mĂ©diĂ©es par les RUV, l'apoptose des kĂ©ratinocytes et une rĂ©gulation Ă tendance positive de l'effet catagĂšne induit par le facteur de croissance.
Conclusion
Notre étude souligne la pertinence clinique de notre dosage d'irradiation UV ex vivo du cuir chevelu et fournit la premiÚre preuve que le rayonnement UV transépidermique affecte négativement d'importantes fonctions du FP chez l'homme. Cela suggÚre que l'intégration d'agents photoprotecteurs des FP tels que la caféine dans les formulations cosmétiques et nutraceutiques des écrans solaires pourrait constituer une stratégie prophylactique sensée
The AHR represses nucleotide excision repair and apoptosis and contributes to UV-induced skin carcinogenesis
Ultraviolet B (UVB) radiation induces mutagenic DNA photoproducts, in particular cyclobutane pyrimidine dimers (CPDs), in epidermal keratinocytes (KC). To prevent skin carcinogenesis, these DNA photoproducts must be removed by nucleotide excision repair (NER) or apoptosis. Here we report that the UVB-sensitive transcription factor aryl hydrocarbon receptor (AHR) attenuates the clearance of UVB-induced CPDs in human HaCaT KC and skin from SKH-1 hairless mice. Subsequent RNA interference and inhibitor studies in KC revealed that AHR specifically suppresses global genome but not transcription-coupled NER. In further experiments, we found that the accelerated repair of CPDs in AHR-compromised KC depended on a modulation of the p27 tumor suppressor protein. Accordingly, p27 protein levels were increased in AHR-silenced KC and skin biopsies from AHR-/- mice, and critical for the improvement of NER. Besides increasing NER activity, AHR inhibition was accompanied by an enhanced occurrence of DNA double-strand breaks triggering KC apoptosis at later time points after irradiation. The UVB-activated AHR thus acts as a negative regulator of both early defense systems against carcinogenesis, NER and apoptosis, implying that it exhibits tumorigenic functions in UVB-exposed skin. In fact, AHR-/- mice developed 50% less UVB-induced cutaneous squamous cell carcinomas in a chronic photocarcinogenesis study than their AHR+/+ littermates. Taken together, our data reveal that AHR influences DNA damage-dependent responses in UVB-irradiated KC and critically contributes to skin photocarcinogenesis in mice