UVB Exposure Research Articles

Mutant p53 reactivator SLMP53-2 hinders ultraviolet B radiation-induced skin carcinogenesis

The growing incidence of skin cancer (SC) has prompted the search for additional preventive strategies to counteract this global health concern. Mutant p53 (mutp53), particularly with ultraviolet radiation (UVR) signature, has emerged as a promising target for SC prevention based on its key role in skin carcinogenesis. Herein, the preventive activity of our previously disclosed mutp53 reactivator SLMP53-2 against UVR-induced SC was investigated. The pre-treatment of keratinocyte HaCaT cells with SLMP53-2, before UVB exposure, depleted mutp53 protein levels with restoration of wild-type-like p53 DNA-binding ability and subsequent transcriptional activity. SLMP53-2 increased cell survival by promoting G1-phase cell cycle arrest, while reducing UVB-induced apoptosis through inhibition of c-Jun N-terminal kinase (JNK) activity. SLMP53-2 also protected cells from reactive oxygen species and oxidative damage induced by UVB. Moreover, it enhanced DNA repair through upregulation of nucleotide excision repair pathway and depletion of UVB-induced DNA damage, as evidenced by a reduction of DNA in comet tails, γH2AX staining and cyclobutane pyrimidine dimers (CPD) levels. SLMP53-2 further suppressed UVB-induced inflammation by inhibiting the nuclear translocation and DNA-binding ability of NF-κB, and promoted the expression of key players involved in keratinocytes differentiation. Consistently, the topical application of SLMP53-2 in mice skin, prior to UVB irradiation, reduced cell death and DNA damage. It also decreased the expression of inflammatory-related proteins and promoted cell differentiation, in UVB-exposed mice skin. Notably, SLMP53-2 did not show signs of skin toxicity for cumulative topical use. Overall, these results support a promising protective activity of SLMP53-2 against UVB-induced SC.

Growth, DMS and DMSP production in Emiliania huxleyi under elevated CO2 and UV radiation

The effects of ocean acidification and solar radiation on marine organisms have received increasing attention. Coccolithophores are a major producer of dimethylsulfoniopropionate (DMSP), which is a precursor of dimethylsulfide (DMS), a volatile biogenic active gas related to climate. Here, we investigated the individual and combined effects of elevated CO2 and ultraviolet radiation (UVR) on growth, DMS, and DMSP production of Emiliania huxleyi. Elevated CO2 (1000 μatm, HC) decreased the cell concentration, DMS, and particulate DMSP (DMSPp) concentrations by 17%, 20%, and 13%, respectively, compared with ambient CO2 (400 μatm, LC) in the semi-continuous culture. The addition of UVA to photosynthetically active radiation (PAR) increased cell concentration of E. huxleyi by 16% on day 4, which may be due to the photorepair effects induced by UVA, and the effect was time-dependent. PAR + UVA and PAR + UVA + UVB exposure decreased cellular DMS by 25%–56%, and increased cellular DMSPp by 60%–130% compared with PAR on days 3–4. Cellular DMSPp followed the order: PAR + UVA > PAR + UVA + UVB > PAR, and HC had no significant effects on cellular DMSPp compared with LC in the combined experiment. These results aid our understanding of the effects of ocean acidification and UV radiation on the production of methyl sulfur compounds in the ocean.

Influence of UV-B treatment on the accumulation of free phenols and tannins in the legumes of Abrus precatorius L. and Vigna mungo (L.) Hepper

BackgroundUltraviolet B radiation with a wavelength from 280 to 320 nm (UV-B) is a prime abiotic factor and environmental stress that can trigger the accumulation/increase of secondary metabolites like phenolic compounds that are unique sources of pharmaceuticals. The Fabaceae family legume seeds or grains contain different kinds of bioactive compounds chiefly classified under phenolic compounds whose potential benefits to human health need to be evaluated for their orderly utilization. This paper aims to study the influence of UV-B radiation on the increase of total free phenols and tannins in the seeds of a wild legume and a crop legume (Abrus precatorius L. and Vigna mungo (L.) Hepper) as a process of fortifying the levels of these bioactive secondary metabolites. MethodThe flour of raw seeds, UV-B exposed raw seeds, soaked seeds, and UV-B exposed soaked seeds of Abrus precatorius and Vigna mungo was used to study the influence of UV-B on the accumulation/increase of total free phenols and tannins in the seeds selected for this study. ResultsBoth raw (dry) and overnight soaked seeds showed increased levels of total free phenols and tannins in response to UV-B exposure. ConclusionIt is concluded that UV-B radiation-related stress (an external stimulus) will have a major influence on the accumulation/increase of secondary metabolites in higher plants.

The effects of UVB irradiance on aberrant epidermal proliferation: Novel insights on how to improve currently available sunscreens

AimsSunscreen use, which prolonged the time required to develop sunburn by reducing the irradiance (mW/cm2) of the UVB radiation, is thought to protect the skin from developing cancers. Recently, in addition to fluence (mJ/cm2), irradiance of the UVB radiation was demonstrated to play an important role leading to photocarcinogenesis of the skin. After equivalent fluence of UVB exposure, enhanced aberrant keratinocyte proliferation contributes significantly to the photocarcinogenic capacity of low irradiance (LI) UVB as compared to its high irradiance (HI) UVB counterpart. However, the mechanism involved remains unclear. Main methodsRelevant cell and animal models were employed to investigate the effects of equivalent UVB fluence administered at HI or LI on keratinocyte proliferation. Additionally, the mechanisms involved were also explored. Key findingsWe found that at equivalent fluence, LIUVB induces significantly higher reactive oxidative species (ROS) production, cell proliferation, as well as phosphorylated AKT (pAKT) expression in both cell and animal models as compare to its HIUVB counterpart. Pretreating cultured keratinocytes with antioxidant or AKT inhibitor significantly reduced the UVB-induced ROS, cell proliferation, and pAKT expression. Additionally, these pretreatments abrogate the difference between the LI and HIUVB treated keratinocytes. Similar findings were noted using animal model treated with AKT inhibitor. SignificanceIn summary, at equivalent fluence, LIUVB induces significantly more aberrant epidermal proliferation via enhanced ROS and pAKT signaling. Reducing UVB-induced AKT phosphorylation presents a novel strategy to improve the protective capacity of the currently available sunscreens.

Accelerated Aging Effect on Mechanical Properties of Common 3D-Printing Polymers.

In outdoor environments, the action of the Sun through its ultraviolet radiation has a degrading effect on most materials, with polymers being among those affected. In the past few years, 3D printing has seen an increased usage in fabricating parts for functional applications, including parts destined for outdoor use. This paper analyzes the effect of accelerated aging through prolonged exposure to UV-B on the mechanical properties of parts 3D printed from the commonly used polymers polylactic acid (PLA) and polyethylene terephthalate–glycol (PETG). Samples 3D printed from these materials went through a dry 24 h UV-B exposure aging treatment and were then tested against a control group for changes in mechanical properties. Both the tensile and compressive strengths were determined, as well as changes in material creep characteristics. After irradiation, PLA and PETG parts saw significant decreases in both tensile strength (PLA: −5.3%; PETG: −36%) and compression strength (PLA: −6.3%; PETG: −38.3%). Part stiffness did not change significantly following the UV-B exposure and creep behavior was closely connected to the decrease in mechanical properties. A scanning electron microscopy (SEM) fractographic analysis was carried out to better understand the failure mechanism and material structural changes in tensile loaded, accelerated aged parts.

Using food fortification to improve vitamin D bioaccessibility and intakes.

Vitamin D intakes and status are low in many countries due to seasonal UVB exposure variation and the fact that few foods are naturally vitamin D rich. Data modelling studies show that vitamin D intakes increase with food fortification, and countries with mandatory fortification policies have higher vitamin D intakes and status compared to countries without. While many foods can be vitamin D fortified, vitamin D bioavailability differs depending on fortification methods, food structure and composition. Randomised controlled trials (RCT) report that vitamin D2 bioavailability varies between foods, whereas vitamin D3 is bioavailable from many foods. In vitro studies suggest that altering the lipid composition of fortified foods increases vitamin D3 absorption. Olive oil increased vitamin D3 absorption during in vitro digestion compared to other dietary oils. Additionally, when vitamin D3 was incorporated into micelles formed from in vitro digestion of olive oil, more vitamin D3 was absorbed compared to other dietary oils. However, in a human postprandial study, a preformed vitamin D3 micelle dairy drink did not increase vitamin D3 absorption, and a vitamin D3 olive dairy drink increased vitamin D3 absorption in vitamin D insufficient participants only. Action is urgently needed to improve vitamin D intakes and status worldwide. Food fortification improves vitamin D intakes; however, fortification strategies unique to each country are needed. This review will synthesise the literature describing data modelling and intervention trials that assess the safety and efficacy of vitamin D fortification strategies, and those manipulating food composition to alter vitamin D bioavailability from fortified foods. Additionally, RCT examining the impact of vitamin D fortification strategies on vitamin D intakes and status over time are reviewed.

Control of end‐of‐life oxygen‐containing groups accumulation in biopolyesters through introduction of crosslinked polysaccharide particles

AbstractThe formulation of bio‐based materials with good performance in service and controlled end‐of‐life is imperative for an effective circular economy. In this work, an innovative approach to induce and control the end‐of‐life of biodegradable polyesters through introduction of crosslinked polysaccharide particles is proposed. Chitosan (Ch) has been subjected to ionotropically crosslinking and then added to polylactic acid (PLA) at different amounts (1.0–4.0%w) by melt mixing. All obtained results suggest that the addition of crosslinked Ch (cCh) particles does not modify significantly the investigated biopolyester properties. Specifically, the thermal analysis of the composites reveals that the addition of unmodified Ch alters the PLA thermal behavior, while the addition of cCh particles does not change the PLA glass transition, cold crystallization and fusion phenomena. The infrared and UV–visible spectroscopic analyses suggest no significant changes in PLA structure. PLA/cCh films show a good optical transparency, which is a desirable property for food packaging applications. In addition, thin PLA‐based films have been subjected to UVB exposure and the accumulation of oxygen‐containing groups has been monitored in time through spectroscopic analysis. Interestingly, at low exposure time, the presence of chitosan slows down the accumulation of these groups, while at long exposure time, chitosan induces accelerated oxygen‐groups formation, supporting its beneficial effect as end‐of‐life accelerant.

Insights into the impact of increasing temperature, light intensity, and UV-B exposure on the circadian rhythm of microcystin production and release, and the expression of mcy genes in the cyanobacterium Microcystis aeruginosa

Insights into the impact of increasing temperature, light intensity, and UV-B exposure on the circadian rhythm of microcystin production and release, and the expression of mcy genes in the cyanobacterium Microcystis aeruginosa

Mycosporine-alanine, an oxo-mycosporine, protect Hassallia byssoidea from high UV and solar irradiation on the stone monument of Konark.

Mycosporine-like amino acids (MAAs) are small natural molecules having potent UV-absorbing and antioxidant properties. Hassallia byssoidea is one dominant cyanobacterium found all over the Konark stone monument, a UNESCO World Heritage site. We characterized mycosporine-alanine for the first time from H. byssoidea and studied its biosynthetic pathway from the whole genome data. We found D-alanyl-D-alanine carboxypeptidase, which might convert mycosporine-glycine to mycosporine-alanine by replacing glycine with alanine or by separate methylation, the mycosporine-glycine is converted to mycosporine-alanine. Our in vitro UV-B exposure experiment and exposure of H. byssoidea to natural sunlight show an increase in biosynthesis of mycosporine-alanine with 12h of UV-B irradiation and high natural sunlight. We also found mycosporine-alanine to have good free radical scavenging activity with an IC50 value of 1.98mg/ml. Our results show due to the presence of mycosporine-alanine H. byssoidea probably tolerate the UV and high solar radiation and continue to colonize on the Konark stone monument as a dominant cyanobacterium.

Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage.

Excessive UV-B exposure is well known to be a risk factor for corneal phototoxicity including direct DNA damage and disturbances in the antioxidant balance. Here, we showed a successful synthesis of a water-soluble and biocompatible small molecule DHPM 1 with dihydropyrimidinthione skeleton, which could effectively protect human corneal epithelial (HCE-2) cells from UV-B damage. In separate experiments, DHPM 1 absorbed UV-B rays and exhibited scavenging activity against intracellular ROS induced by UV-B radiation, thereby reducing the levels of DNA fragmentation. Additionally, UV-B exposure increased the expression of cleaved caspase-3, as well as the ratio of Bax/Bcl-2 at protein levels, while pretreatment with DHPM 1 significantly reversed these changes. To the best of our knowledge, this is the first report of a study based on dihydropyrimidinthione derivatives to develop a promising eye drops, which may well find extensive applications in UV-B caused corneal damage.

Amphiphilic and Biocompatible DNA Origami-Based Emulsion Formation and Nanopore Release for Anti-Melanogenesis Therapy.

Programmable engineered DNA origami provides infinite possibilities for customizing nanostructures with controllable precision and configurable functionality. Here, a strategy for fabricating an amphiphilic triangular DNA origami with a central nanopore that integrates phase-stabilizing, porous-gated, and affinity-delivering effects is presented. By introducing the DNA origami as a single-component surfactant, the water-in-oil-in-water (W/O/W) emulsion is effectively stabilized with decreased interfacial tension. Microscopic observation validates the attachment of the DNA origami onto the water-in-oil and oil-in-water interfaces. Furthermore, fluorescence studies and molecular docking simulations indicate the binding interactions of DNA origami with arbutin and coumaric acid at docking sites within central nanopores. These central nanopores are functionalized as molecular gates and affinity-based scaffold for the zero-order release of arbutin and coumaric acid at a constant rate regardless of concentration gradient throughout the whole releasing period. In vivo zebrafish results illustrate the advantages of this zero-order release for anti-melanogenesis therapy over direct exposure or Fickian diffusion. The DNA origami-based W/O/W emulsion presents anti-melanogenic effects against UV-B exposure without cardiotoxicity or motor toxicity. These results demonstrate that this non-toxic amphiphilic triangular DNA origami is capable of solely stabilizing the W/O/W emulsion as well as serving as nanopore gates and affinity-based scaffold for constant release.

Evaluating Whether Radiofrequency Irradiation Attenuated UV-B-Induced Skin Pigmentation by Increasing Melanosomal Autophagy and Decreasing Melanin Synthesis.

Autophagy is involved in the degradation of melanosomes and the determination of skin color. TLR4 and tumor necrosis factor (TNF) signaling upregulates NF-kB expression, which is involved in the upregulation of mTOR. The activation of mTOR by UV-B exposure results in decreased autophagy, whereas radiofrequency (RF) irradiation decreases TLR4 and TNF receptor (TNFR) expression. We evaluated whether RF decreased skin pigmentation by restoring autophagy by decreasing the expression of TLR4 or TNFR/NF-κB/mTOR in the UV-B-irradiated animal model. UV-B radiation induced the expressions of TNFR, TLR, and NF-κB in the skin, which were all decreased by RF irradiation. RF irradiation also decreased phosphorylated mTOR expression and upregulated autophagy initiation factors such as FIP200, ULK1, ULK2, ATG13, and ATG101 in the UV-B-irradiated skin. Beclin 1 expression and the expression ratio of LC3-I to LC3-II were increased by UV-B/RF irradiation. Furthermore, melanin-containing autophagosomes increased with RF irradiation. Fontana-Masson staining showed that the amount of melanin deposition in the skin was decreased by RF irradiation. This study showed that RF irradiation decreased skin pigmentation by restoring melanosomal autophagy, and that the possible signal pathways which modulate autophagy could be TLR4, TNFR, NF-κB, and mTOR.

Hesperidin Inhibits UVB-Induced VEGF Production and Angiogenesis via the Inhibition of PI3K/Akt Pathway in HR-1 Hairless Mice.

Hesperidin is a citrus flavanone glycoside with potent anti-inflammatory effects that interferes with UVB-stimulated angiogenesis in skin, but its molecular mechanisms of action remain unclear. Here, we investigated the effects of hesperidin on UVB-induced angiogenesis in HR-1 hairless mice. We found hesperidin treatment inhibited skin neovascularization skin induced by repetitive UVB light exposure. Exposure to UVB radiation induces the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-13 (MMP-13), and MMP-9, but we found all of these were inhibited by treatment with hesperidin. Using immunohistochemistry and Western blotting, we also found hesperidin inhibited the increase in hypoxia inducible factor-1 (HIF-1)α expression induced by UVB exposure. After discovering that UVB induces VEGF expression via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathways, we found hesperidin reduces UVB-induced VEGF expression by inhibiting UVB-induced PI3K activity. This, in turn, reduces the UVB-induced Akt/p70S6K phosphorylation in human primary keratinocytes and fibroblast cells. Because it affects the mediators of angiogenesis, our data suggest hesperidin has an anti-angiogenic effect on the pathologic skin neovascularization induced by UVB light. Thus, hesperidin may prove useful in the treatment of skin injuries caused by UVB light exposure.

β-Nicotinamide Mononucleotide (NMN) Administrated by Intraperitoneal Injection Mediates Protection Against UVB-Induced Skin Damage in Mice.

ObjectiveUltraviolet light is an important environmental factor that induces skin oxidation, inflammation, and other diseases. Nicotinamide mononucleotide (NMN) has the effect of anti-oxidation and improving various physiological processes. This study explores the protective effect of NMN monomers given via intraperitoneal injection on UVB-induced photodamage.MethodsWe used a murine model of UVB-induced photodamage to evaluate the effect of an NMN monomer on photoaging skin by assessing skin and liver tissue sections, serum and skin oxidative stress levels, inflammatory markers, mRNA expression, and protein expression of skin- and liver-related genes.ResultsThe results showed that NMN treatment blocked UVB-induced photodamage in mice, maintaining normal structure and amount of collagen fibers, normal thickness of epidermis and dermis, reducing the production of mast cells, and maintaining complete organized skin structure. NMN intraperitoneal injection also maintained the normal morphology of the mouse liver after UVB exposure. Meanwhile, NMN intraperitoneal injection was found to increase antioxidant ability and regulate the proinflammatory response of the skin and liver to UVB irradiation by enhancing the activity of antioxidant enzymes, release of anti-inflammatory cytokines, reduction of hydrogen peroxide production (H2O2), and decreased inflammatory cytokines. Furthermore, RT-qPCR results indicated that NMN reduced oxidative stress of skin and liver by promoting the activation of the AMP-activated protein kinase (AMPK) signaling pathway and further increasing the expression of downstream antioxidant genes of AMPK. RT-qPCR results also revealed that NMN treatment could downregulate the mRNA expression of interleukin (IL)-6, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, and upregulate NF-kappa-B inhibitor-α (IκB-α) and interleukin (IL)-10 by inhibiting the activation of nuclear factor-κBp65 (NFκB-p65). Finally, NMN upregulated AMPK, IκB-α, SOD1, and CAT in the skin and downregulated NF-κBp65 protein expression, which is in line with the RT-qPCR results.ConclusionBased on the above results, NMN monomer treatment with intraperitoneal injection also block the photodamage caused by UVB irradiation in mice by regulating the oxidative stress response and inflammatory response.

313 Photoprotective effects of liposomal DNA repair enzymes are independent of its effect on the microbiome

Solar ultraviolet radiation (UVR) is a mutagenic agent causing damage to the DNA and resulting in photoageing and carcinogenesis. Polymorphic light eruption (PLE) is a frequent skin disorder characterized by the appearance of itchy polymorphic skin lesions (photodermatosis) which is triggered by natural sunlight. In our previous study, PLE patients treated with liposomal DNA repair enzymes diminished induction of PLE symptoms, however the underlying mechanisms remained unraveled. We now investigated whether the therapeutic potential of topical DNA repair enzymes is due to its effect on the skin resident microbes, which are also impacted by UV exposure. To test this hypothesis, we investigated the effect of DNA repair enzymes (photolyase from Anacystis nidulans and Micrococcus luteus extract with endonuclease activity) on the survival of commensal skin microbes subjected to UVB radiation. Briefly, strains of microbes (Staphylococcus aureus or S. epidermidis) were cultured and exposed to varying doses of UVB. DNA repair enzymes incorporated in liposomes or vehicle (liposomes alone) were added to the culture medium/plate either before or after UVB exposure, followed by photoactivating visible (blue) light exposure or not in the case of photolyase administration. The colony forming units of the cultures was quantified throughout the protocol. The results showed no significant difference in the survival of either the pathogenic or the commensal bacterial strain treated with liposomal DNA repair enzymes following exposure to UVB radiation. Taken together, this data suggests that photoprotective effect of DNA repair enzymes is independent of its direct activity on the skin microbiome.

Randomized controlled trial of fractionated laser resurfacing on aged skin as prophylaxis against actinic neoplasia.

BACKGROUNDThe loss of insulin-like growth factor 1 (IGF-1) expression in senescent dermal fibroblasts during aging is associated with an increased risk of nonmelanoma skin cancer (NMSC). We tested how IGF-1 signaling can influence photocarcinogenesis during chronic UVB exposure to determine if fractionated laser resurfacing (FLR) of aged skin, which upregulates dermal IGF-1 levels, can prevent the occurrence of actinic keratosis (AK) and NMSC.METHODSA human skin/immunodeficient mouse xenografting model was used to test the effects of a small molecule inhibitor of the IGF-1 receptor on chronic UVB radiation. Subsequently, the durability of FLR treatment was tested on a cohort of human participants aged 65 years and older. Finally, 48 individuals aged 60 years and older with considerable actinic damage were enrolled in a prospective randomized clinical trial in which they underwent a single unilateral FLR treatment of one lower arm. Numbers of AKs/NMSCs were recorded on both extremities for up to 36 months in blinded fashion.RESULTSXenografting studies revealed that chronic UVB treatment with a topical IGF-1R inhibitor resulted in a procarcinogenic response. A single FLR treatment was durable in restoring appropriate UVB response in geriatric skin for at least 2 years. FLR resulted in sustained reduction in numbers of AKs and decreased numbers of NMSCs in the treated arm (2 NMSCs) versus the untreated arm (24 NMSCs).CONCLUSIONThe elimination of senescent fibroblasts via FLR reduced the procarcinogenic UVB response of aged skin. Thus, wounding therapies are a potentially effective prophylaxis for managing high-risk populations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03906253).FUNDINGNational Institutes of Health, Veterans Administration.

Antiaging and Skin Irritation Potential of Four Main Indonesian Essential Oils

Essential oils possess antiaging properties due to their antioxidant activity. This study aims to determine the antiaging activities of four main Indonesian essential oils and their irritation potential on the skin. The spot yeast and in vivo rat skin with UVB exposure methods were used to analyze the antiaging activity of essential oils on aging triggered by endogenous and exogenous factors, respectively. Meanwhile, patch tests and clinical evaluations were used for the skin irritation potential analysis. The antiaging activity results from the endogenous factor showed that the use of clove, patchouli, nutmeg, and citronella oils increased yeast viability at concentrations of 20, 40, 60, and 100 µg/mL, respectively. Furthermore, nutmeg, cloves, citronella, and patchouli oils decreased the wrinkle score on rat skin after UVB exposure (exogenous factor). The skin irritation potential results of patchouli, nutmeg, citronella, and clove oils were none (0), slightly (0.02), moderately (0.09), and very irritating (0.39), respectively.

Gum Arabic-induced oral photoprotection: Shifting the balance against circulating immune suppressive cytokines

Oral dietary botanicals are gaining considerable attention as complementary measures for photoprotection. Gum Arabic (GA) is a natural dietary fibre known for its potent antioxidant and immunomodulatory effects. We sought to evaluate the efficacy of GA as an oral photo- protective agent by assessing the effect of regular GA consumption on ultraviolet radiation (UVR)-induced systemic imbalance in circulating cytokines and T lymphocyte populations. The study included six groups of mice (n=10/group): Control group; GA group =Mice on GA supplementation (20 g/kg/day for 28 days); group 3 and 4=Mice exposed to sunlight, mice in group 4 were on GA supplementation (sunUVR+ GA); group 5 and 6=Mice exposed to ultraviolet B, mice in group 6 were on GA supplementation (UVB+GA). UVR exposure was conducted during the last four days of a 28 days follow-up period as follows: 30 minutes/day for sunlight exposure and 20 minutes/day for UVB. Plasma cytokines were measured using ELISA, and blood CD4+ and CD8+ T lymphocytes and the CD4/CD8 ratio were evaluated using flow cytometry. Mice exposed to sunlight and UVB following a period of GA supplementation had lower levels of anti-inflammatory cytokines (IL-10 and TGF-β) and higher levels of proinflammatory cytokines (IL-12, IFN-γ, and TNF-α) than mice exposed to radiation without prior GA intake. GA supplementation significantly increased the proportion of CD8 in sun exposure group, and the proportion of CD4 in UVB exposure group. In conclusion, GA intake tipped the balance of circulating cytokines in favour of proinflammatory cytokines; therefore, it attenuated UVR-induced immunosuppression. The photo protective effects of GA detected might be attributed to increased circulating short chain fatty acids (SCFA) from GA colonic fermentation. GA is a potential candidate for oral photoprotection.

Keratinocytes Counteract UVB-Induced Immunosuppression in Mice through HIF-1a Signaling

The transcription factor HIF-1a regulates cellular metabolism under hypoxia but also immune responses and UVB-induced skin reactions. In keratinocytes (KCs), HIF-1a is an environmental sensor orchestrating the adaptation to environmental changes. In this study, we investigated the role of HIF-1a in KCs for skin reactions to acute and chronic UVB exposure in mice. The function of HIF-1a in KCs under UVB exposure was analyzed in KC-specific HIF-1a conditional knockout (cKO) mice. cKO mice were hypersensitive to acute high-dose UVB irradiation compared with wild-type mice, displaying increased cell death and delayed barrier repair. After chronic low-dose UVB treatment, cKO mice also had stronger epidermal damage but reduced infiltration of dermal macrophages and T helper cells compared with wild-type mice. Irradiated cKO mice revealed accumulation of regulatory lymphocytes in dorsal skin-draining lymph nodes compared with wild-type and unirradiated mice. This was reflected by an augmented IL-10 release of lymph node cells and a weaker contact hypersensitivity reaction to DNFB in UVB-exposed cKO mice than in wild-type and unirradiated controls. In summary, we found that KC-specific HIF-1a expression is crucial for adaptation to UVB exposure and inhibits the development of UVB-induced immunosuppression in mice. Therefore, HIF-1a signaling in KCs could ameliorate photoaging-related skin disorders.

Keratinocyte death by ferroptosis initiates skin inflammation after UVB exposure

The ultraviolet B radiation (UVB) causes skin inflammation, which contributes to the causality and the exacerbation of a number of cutaneous diseases. However, the mechanism of UVB-driven inflammation in the skin remains poorly understood. We show that ferroptosis, a non-apoptotic programmed cell death pathway that is promoted by an excessive phospholipid peroxidation, is activated in the epidermal keratinocytes after their exposure to UVB. The susceptibility of the keratinocytes to UVB-induced ferroptosis depends on the extent of pro-ferroptosis death signal generation and the dysregulation of the glutathione system. Inhibition of ferroptosis prevents the release of HMGB1 from the human epidermal keratinocytes, and blocks necroinflammation in the UVB-irradiated mouse skin. We show that while apoptosis and pyroptosis are also detectable in the keratinocytes after UVB exposure, ferroptosis plays a significant role in initiating UVB-induced inflammation in the skin. Our results have important implications for the prevention and the treatment of a broad range of skin diseases which are fostered by UVB-induced inflammation.