Inhibiting Neutrophil Extracellular Traps Protects against Ultraviolet B-Induced Skin Damage: Effects of Hochu-ekki-to and DNase I.

UV-B radiation induces sunburn, and neutrophils are pivotal in this inflammation. In this study, we examined the potential involvement of neutrophil extracellular traps (NETs) in ultraviolet B (UVB)-induced skin inflammation, correlating the skin inflammation-mitigating effects of Hochu-ekki-to on UV-B irradiation and NETs. To elucidate NET distribution in the dorsal skin, male ICR mice, exposed to UVB irradiation, were immunohistologically analyzed to detect citrullinated histone H3 (citH3) and peptidylarginine deiminase 4 (PAD4). Reactive oxygen species (ROS) production in the bloodstream was analyzed. To establish the involvement of NET-released DNA in this inflammatory response, mice were UV-B irradiated following the intraperitoneal administration of DNase I. In vitro experiments were performed to scrutinize the impact of Hochu-ekki-to on A23187-induced NETs in neutrophil-like HL-60 cells. UV-B irradiation induced dorsal skin inflammation, coinciding with a significant increase in citH3 and PAD4 expression. Administration of DNase I attenuated UV-B-induced skin inflammation, whereas Hochu-ekki-to administration considerably suppressed the inflammation, correlating with diminished levels of citH3 and PAD4 in the dorsal skin. UV-B irradiation conspicuously augmented ROS and hydrogen peroxide (H2O2) production in the blood. Hochu-ekki-to significantly inhibited ROS and H2O2 generation. In vitro experiments demonstrated that Hochu-ekki-to notably inhibited A23187-induced NETs in differentiated neutrophil-like cells. Hence, NETs have been implicated in UV-B-induced skin inflammation, and their inhibition reduces cutaneous inflammation. Additionally, Hochu-ekki-to mitigated skin inflammation by impeding neutrophil infiltration and NETs in the dorsal skin of mice.

Tranexamic acid reduces endometrial cancer effects through the production of angiostatin.

Tranexamic acid (TA) has been reported to exhibit antitumor effects in various mouse models of cancer. However, the mechanism underlying its antitumor effects against endometrial cancer remains to be elucidated. This study was aimed at investigating the efficacy of TA against chronic inflammation-associated endometrial cancer induced by N-methyl-N-nitrosourea (MNU) and estradiol in a mouse model. After cancer induction, the mice were administered TA (12 mg/kg) three times weekly during the experimental period. The endometrial cancer development induced by MNU and estradiol was ameliorated by TA administration. Furthermore, TA treatment suppressed the levels of carbohydrate antigen 125, interleukin-6, and tumor necrosis factor-α in the plasma. The level of plasminogen, known as a TA target, increased in endometrial cancer and was further increased by TA treatment. On the other hand, plasmin levels increased in the model mice but decreased after TA treatment. Furthermore, the macrophage counts and the levels of matrix metalloproteinase (MMP)-12 and angiostatin in tumor cells in the uterus increased compared to the corresponding values in the control group and further increased upon TA treatment. The results of our study indicate that TA ameliorated the endometrial cancer induced by MNU and estradiol by regulating the macrophage/MMP-12/plasminogen/angiostatin signal transmission pathway.

Glycyrrhizin ameliorates melanoma cell extravasation into mouse lungs by regulating signal transduction through HMGB1 and its receptors.

Metastasis, which accounts for the majority of all cancer-related deaths, occurs through several steps, namely, local invasion, intravasation, transport, extravasation, and colonization. Glycyrrhizin has been reported to inhibit pulmonary metastasis in mice inoculated with B16 melanoma. This study aimed to identify the mechanism through which glycyrrhizin ameliorates the extravasation of melanoma cells into mouse lungs. Following B16 melanoma cell injection, mice were orally administered glycyrrhizin once every two days over 2 weeks; lung samples were then obtained and analyzed. Blood samples were collected on the final day, and cytokine plasma levels were determined. We found that glycyrrhizin ameliorated the extravasation of melanoma cells into the lungs and suppressed the plasma levels of interleukin-6, tumor necrosis factor-α, and transforming growth factor-ß. Furthermore, glycyrrhizin ameliorated the lung tissue expression of high mobility group box-1 protein (HMGB1), receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)-4, RAS, extracellular signal-related kinase, NF-κB, myeloid differentiation primary response 88, IκB kinase complex, epithelial-mesenchymal transition markers, and vascular endothelial growth factor-A. Our study demonstrates that glycyrrhizin ameliorates melanoma metastasis by regulating the HMGB1/RAGE and HMGB1/TLR-4 signal transduction pathways.

Tranexamic Acid Improves Memory and Learning Abilities in Aging Mice.

PURPOSE: Although the onset mechanism of Alzheimer's disease, which co-occurs with aging, has been extensively studied, no effective methods that improve the decline in memory and learning abilities following aging have been developed. Tranexamic acid provided promising results for ameliorating photo-aging and extending the natural lifespan. However, it is unknown whether it affects the decline in memory and learning abilities due to aging. In this study, we examined the effect of tranexamic acid on memory and learning abilities of naturally aging mice. METHODS: ICR mice were orally administered with tranexamic acid (12 mg/kg/day) three times weekly for 2 years, and their memory and learning abilities were compared between the tranexamic acid-treated and non-treated groups. RESULTS: The decline in memory and learning abilities due to aging was ameliorated by tranexamic acid administration. The expression of plasmin and amyloid-ß decreased following the treatment with tranexamic acid. Furthermore, the number of M1-type brain macrophages diminished and that of M2 macrophages increased. In addition, administration of tranexamic acid decreased the concentrations of interleukin (IL)-1ß and tumor necrosis factor-α, while it increased the levels of IL-10 and transforming growth factor-α in the brain. CONCLUSION: These results indicated that tranexamic acid suppressed the secretion of the inflammatory cytokines aging M1-type macrophages, thereby improving age-related memory and learning abilities.

Role of Momordica charantia in preventing the natural aging process of skin and sexual organs in mice.

Although various methods for improving the natural aging of skin have been examined, an effective method is currently unavailable. Therefore, in this study, we investigated the effects of Momordica charantia on the natural aging of skin of mice and how sex differences influenced these effects. To this end, we bred female and male hairless mice without ultraviolet ray irradiation and physical stress for 2 years. During the study period, mice were orally administered 50 mg/kg/day Momordica charantia fruit extract, three times per week. The characteristics of naturally aging skin, in terms of moisture retention, hydration, thickness, and reduced wrinkle score, improved after Momordica charantia treatment in both male and female mice. Furthermore, reduced cell apoptosis was observed in the female ovaries and male testes, and the levels of testosterone and 17ß-estradiol in blood were maintained. After treatment with Momordica charantia, the expression of matrix metalloprotease (MMP)-1 and hyaluronidase (HAYL)2 decreased in the skin of female mice, whereas the serum levels of interleukin (IL)-33 increased in the male mice. These results indicated that the natural aging of the skin was decelerated by Momordica charantia via regulation of the 17ß-estradiol/mast cell/MMP-1/HAYL2 and testosterone/mast cell/IL-33 signaling pathways in female and male mice, respectively.

Ameliorative effect of green odor against UVB-induced immunosuppression of contact hypersensitivity.

Ultraviolet (UV) irradiation to the eye induces photoimmunosuppression. In here, we examined the effect of green odor against immunosuppression of contact hypersensitivity in the eye induced by ultraviolet B (UVB) irradiation. Systemic immunosuppression was induced in ICR mice sensitized with 0.5% oxazolone through the skin by a single exposure to UVB. Consecutive green odor treatment significantly counteracted UVB irradiation-induced immunosuppression of the contact hypersensitivity (CHS) response. The green odor treatment increased dopamine and ß-endorphin levels in the brain and the plasma, respectively, and decreased the plasma corticosterone concentration in the oxazolone-sensitized mice after UVB irradiation to the eye, in contrast with that in acetone-treated mice (treatment negative control). Green odor prevented UVB irradiation-induced photoimmunosuppression of the CHS response by regulating the dopamine/ß-endorphin/corticosterone pathway.

Long-term UVA exposure to the eye compromises memory and learning ability in mice via corticotropin-releasing hormone type 2 receptor.

Long-term eye exposure to ultraviolet (UV)A can effect memory and learning ability. However, the underlying mechanism behind these effects remain unknown. In this study, we used HR-1 mice to study effects of long-term UVA eye irradiation. The eyes or dorsal skin of the mice were exposed to UVA at the dose of 110kj/m2 using an FL20SBLB-A lamp three times a week over 12 months. We measured the levels of reactive oxygen species, corticotropin-releasing hormone (CRH), urocortin 2, and CRH type 2 receptor (CRHR-2) in the brain of treated and control animals. Their memory and learning ability following exposure to UVA was analyzed by the standard water maze test. Our results showed that the levels of reactive oxygen species, CRH, urocortin 2, and CRHR-2 increased significantly following long-term UVA irradiation, and the effects were more pronounced in animals subjected to eye irradiation than those subjected to dorsal skin irradiation. Furthermore, the UVA exposure led to an increase in the levels of ß-amyloid and microglia in the brain. These results indicated that UVA eye irradiation potentially mediated a decline in memory and learning ability via enhancing levels of urocortin 2, microglia, and ß-amyloid in the brain.

Tranexamic Acid Protects Ovary and Testis Functions and Ameliorates Osteoporosis in Mice.

INTRODUCTION: In a rapidly aging society, the number of people suffering from osteoporosis keeps increasing. However, effective prevention strategies for osteoporosis are not yet currently available. OBJECTIVE: In this study, we examined the ameliorative effects of tranexamic acid on osteoporosis in 24-month-old mice. METHODS: During the study period, mice were orally administered tranexamic acid 3 times per week. RESULTS: Bone mineral density, which is a parameter of osteoporosis, was improved following tranexamic acid administration. In addition, female mice evidenced a stronger phenotypic improvement than male mice. In female mice treated with tranexamic acid, ovary abnormalities were reduced. Furthermore, the levels of transforming growth factor-ß, hyaluronic acid, CD44, reactive oxygen species, and apoptosis, as well as the number of infiltrated neutrophils and macrophages in the ovary were lower than those in the control or solvent-administered mice. In addition, 17ß-estradiol levels in blood increased when compared with the control or solvent-treated mice. In addition, administration of tranexamic acid to 24-month-old male mice decreased the level of apoptosis in the testis. However, the levels of 17ß-estradiol and testosterone in blood increased compared with the control or solvent-administered mice. CONCLUSIONS: The use of tranexamic acid had an ameliorative effect on osteoporosis, possibly by protecting ovaries and testes.

Ameliorative Effect of Hochu-ekki-to on Natural Skin Aging.

INTRODUCTION: Although it is beneficial to protect the skin from natural aging, especially in an aging society, the approach by which this can be achieved is still not well known. Hochu-ekki-to, a Chinese natural medicine, has various advantageous effects; however, there is no report about its influence on skin aging. OBJECTIVE: Therefore, we examined the effect of hochu-ekki-to against natural aging. METHODS: Hairless mice, bred without ultraviolet ray irradiation and physical stress, were orally administered huchu-ekki-to 3 times per week for 2 years. After that period, degree of skin hydration and permeability were measured. Furthermore, hematoxylin and eosin histochemistry was performed to determine the morphology and condition of the tissues. Lastly, levels of vitamin A, vitamin C, and reactive oxygen species (ROS) in plasma and skin, as well as concentration of hyaluronic acid in the skin, were measured. RESULTS: Signs of skin aging were ameliorated by administration of hochu-ekki-to, such as moisture retention, skin hydration, and the generation of wrinkles. Furthermore, vitamin A, vitamin C, collagen type I, collagen type III, fibroblasts, and hyaluronic acid levels in the skin increased, while levels of ROS decreased after hochu-ekki-to treatment. CONCLUSION: These results indicated that natural skin aging was ameliorated by treatment with hochu-ekki-to, specifically moisture retention, and skin hydration, and thickening, via the regulation of the vitamin C/fibroblast, collagen type III/collagen type I, and vitamin A/hyaluronic acid signaling pathways.

Effect of tranexamic acid in improving the lifespan of naturally aging mice.

An effective method to improve lifespan is not known. Therefore, in this study, we examined the lifespan-extending effect of tranexamic acid in normal mice. We bred hairless mice without exposure to ultraviolet radiation and psychical stress until they died naturally. During the study period, the mice were orally administered tranexamic acid (12 mg/kg/day) three times weekly. An increase in the lifespan of mice was observed by tranexamic acid administration. Furthermore, age-related diseases of the skin were ameliorated by tranexamic acid administration. Moreover, the blood level of tumor necrosis factor-α, interleukin-6, reactive oxygen species (ROS), and matrix metalloproteinase (MMP)-9 was decreased by tranexamic acid administration. These results indicate that tranexamic acid suppresses the secretion of inflammatory cytokines, MMP-9, and ROS induced by natural aging, ameliorating age-related diseases, and, consequently, extending the lifespan.

The Role of gp91phox and the Effect of Tranexamic Acid Administration on Hair Color in Mice.

We observed that on long-term breeding, gp91phox-knockout (gp91phox-/-) mice developed white hair. Here, we investigate the origin of this hitherto unexplained phenomenon. Moreover, we investigated the effect of tranexamic acid administration on the hair color in gp91phox-/- mice. We administered tranexamic acid (about 12 mg/kg/day) orally to 9-week-old C57BL/6j (control) and gp91phox-/- mice, thrice a week for 12 months. Compared to control mice, gp91phox-/- mice showed more white hair. However, the concentrations of reactive oxygen species and the levels of interleukin (IL)-1ß and transforming growth factor (TGF)-ß in the skin were lower than those in the control group. Furthermore, increase in white hair was observed in the control mice upon administration of the IL-1ß antagonist. On the other hand, administration of tranexamic acid led to brown colored hair on gp91phox-/- mice. Although tranexamic acid treatment did not alter the expression levels of melanocortin receptor 1 and agouti signaling protein on hair follicles, it increased the expression of mahogunin ring finger protein 1 (MGRN1) and collagen XVII. These results suggested that retention of black hair requires the gp91phox/ROS/IL-1ß/TGF-ß pathway and that elevated levels of MGRN1 and collagen XVII lead to brown hair in gp91phox-/- mice.

Ameliorative effect of tranexamic acid on physiological skin aging and its sex difference in mice.

An effective method to protect the skin from natural aging is unknown. Therefore, in this study, we examined the ameliorative effects of tranexamic acid on natural skin aging. In addition, we examined the sex difference in the effect exhibited by tranexamic acid. We bred hairless mice without ultraviolet ray irradiation and physical stress for 2 years. During the study period, mice were orally administered tranexamic acid (12 mg/kg/day) three times per week. Development of signs of skin aging was found to be ameliorated by tranexamic acid. Furthermore, synthetic inhibition of plasmin was observed following tranexamic acid treatment. The synthetic reinforcement of hyaluronic acid by an increase in the number of epidermal cells and the degradative inhibition of extracellular matrix (ECM) by matrix metalloproteinase (MMP) suppression were observed. These results indicate that natural skin aging was ameliorated by tranexamic acid via the regulation of the plasmin/TGF-ß/epidermal cells/hyaluronic acid and plasmin/MMPs/ECM signal transmission pathways. Taken together, sex difference was observed for the ameliorative effect of tranexamic acid on skin aging, with a stronger effect observed in females than in males. More importantly, we found that the synthesis of hyaluronic acid was stronger in female mice than in male mice.

Ameliorative Effect of High-Dose Vitamin C Administration on Dextran Sulfate Sodium-Induced Colitis Mouse Model.

Vitamin C is a natural nutrient with antioxidant properties and is used as a health supplement. In this study, we examined the effects of intraperitoneal administration of high-dose vitamin C (4 g/kg) on dextran sodium sulfate (DSS)-induced ulcerative colitis. We prepared a mouse ulcerative colitis model by administering DSS for 7 d along with high-dose vitamin C each day during DSS treatment. Ulcerative colitis induced by DSS was ameliorated by high-dose vitamin C administration. Blood levels of interleukin-6, tumor necrosis factor-α, hydrogen peroxide (H2O2), and iron were elevated in DSS-treated mice but lowered by high-dose vitamin C administration. Contrarily, the levels of H2O2 and iron and the numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells in the colon were further increased by high-dose vitamin C administration. The expression levels of fibroblasts, collagen type I, and collagen type III decreased in the DSS-treated mice but increased in mice administered high-dose vitamin C. These results suggest that high-dose vitamin C administration can improve ulcerative colitis.

Impaired skin barrier function caused by reactive oxygen species in mice with colonic tumours.

Purpose: We have previously reported that skin barrier function is disrupted in mice with colonic tumours induced by azoxymethane (AOM) and dextran sodium sulphate (DSS). We postulated that the impaired skin barrier function was associated with reactive oxygen species derived from gp91phox. In this study, we investigated the mechanisms underlying the impaired skin barrier function using gp91phox-/- mice. Materials and methods: We induced colonic tumorigenesis in C57BL/6j mice by AOM + DSS administration and evaluated the influence of reactive oxygen species on skin barrier function by using the hydroxyl radical scavenger N-acetyl-l-cysteine (NAC) or gp91phox-/- mice. Damage to the colon and skin following treatment with AOM + DSS was monitored using protein analysis methods and by detection of inflammatory mediators in the plasma. Results: NAC could not prevent the increase in transepidermal water loss (TEWL) and decrease in skin hydration level caused by AOM + DSS in gp91phox+/+ mice. However, gp91phox-/- mice showed no change in TEWL and skin hydration level. The dermal expression levels of nucleotide-binding domain, leucine-rich containing family, pyrin-domain containing 3 (NLRP3), and caspase-1 were reduced in gp91phox-/- mice. Moreover, the plasma concentrations of interleukin-18 and thymic stromal lymphopoietin (TSLP) were lower in gp91phox-/- mice than those in gp91phox+/+ mice. Inhibition of hydrogen peroxide production from superoxide anions in the gp91phox-/- status prevented the increased TEWL and decreased skin hydration level noted with degradation of NLRP3 and caspase-1. Conclusions: Superoxide anions may play an important role in the onset of the impaired skin barrier function in mice with colonic tumours.

Tranexamic Acid Ameliorates Nonmelanoma Skin Cancer Induced by Long-term Ultraviolet A Irradiation.

To date, there have been no treatments developed to ameliorate nonmelanoma skin cancer induced by long-term exposure to ultraviolet A (UVA) irradiation. In this study, we examined the effects of tranexamic acid (trans-4-aminomethyl cyclohexanecarboxylic acid) on long-term UVA-induced skin cancer. We exposed the dorsal skin of male hairless mice to UVA at a dose of 110 kJ m-2 using an FL20SBLB-A lamp three times weekly for 15 weeks after application of 7,12-dimethylbenz [a] anthracene (DMBA). During the experimental period, the mice were administered tranexamic acid (750 mg kg-1 day-1 ) three times weekly. We found that cancer development was ameliorated by administration of tranexamic acid. Furthermore, tranexamic acid treatment was observed to suppress increases in the plasma levels of matrix metalloproteinase-9 and interleukin (IL)-6, and skin expression of plasmin, CC chemokine 2, macrophages, signal transducer and activator of transcription (STAT)3, cyclin D and vascular endothelial growth factor (VEGF)-A that occurred in mice subjected to long-term UVA irradiation. These results indicated that the nonmelanoma skin cancer induced by DMBA+UVA long-term irradiation is ameliorated by tranexamic acid through regulation of the plasmin/macrophage/IL-6/STAT3/cyclin D signal transmission pathway. In addition, this ameliorative effect against skin cancer may be mediated via inhibition of the IL-6-induced expression of VEGF-A.

The Clock Genes Are Involved in The Deterioration of Atopic Dermatitis after Day-and-Night Reversed Physical Stress in NC/Nga Mice.

BACKGROUND: In modern society, irregular lifestyles are a problem. It is well known that Atopic Dermatitis (AD) occurs during physical stress in people with an irregular lifestyle. We evaluated the influence that day-and-night reversal physical stress has on AD. METHODS: Six-week-old specific-pathogen-free and conventional NC/Nga male mice were used. For the day-and-night reversal procedure, the mice ran on a treadmill at a slow speed of 10 m/min for 12 h (between 8:00 and 20:00). Then, between 20:00 and 8:00, we put the mice in a dark place. This treatment was repeated every day for two weeks. The behavioral circadian rhythm of the mice was evaluated with the open field test. Then, the mice were sacrificed and histological examinations of the tissues, the expression of peptide hormones, corticosterone, Immunoglobulin E, histamine, and cytokines was performed using an enzyme-linked immunosorbent assay. RESULTS: In the treadmill-treated conventional NC/Nga mice, AD symptoms were deteriorated compared with the non-treated conventional NC/Nga mice. The levels of Period (Per) 2, Clock, and brain and muscle arnt-like protein 1 (Bmal1) in the skin were increased constantly in the treadmill-treated conventional mice. Furthermore, the expression of Retinoic Acid-related Orphan Receptor (ROR)α, which activates Bmal1, was increased in the treadmill-treated conventional mice compared with the non-treated conventional mice. In addition, when non-treated conventional mice were administrated by the agonist of RORα, AD symptoms were deteriorated similar to treadmill-treated conventional mice. CONCLUSION: In the day-and-night reversal mice, the clock genes were increased constantly, indicating that this is a factor that deteriorated AD.

Tranexamic acid inhibits the plasma and non-irradiated skin markers of photoaging induced by long-term UVA eye irradiation in female mice.

Photoaging can be induced by long-term ultraviolet (UV)A eye irradiation, but an ameliorating method for such photoaging is not known. In this study, we examined the effects of tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) on photoaging of the skin induced by UVA eye irradiation. We used the C57BL/6 j female mice and locally exposed their eyes to UVA at a dose of 110 kJ/m2 using an FL20SBLB-A lamp multiple times a week for one year. The plasma urocortin 2, ß-endorphin, methionine enkephalin (OGF), and histamine content, as well as the expression of the corticotropin-releasing hormone receptor (CRHR) type 2, µ-opioid receptor, opioid growth factor receptor (OGFR), T-bet, and GATA3 increased in the mice subjected to UVA eye irradiation. However, the increased levels of urocortin 2, methionine enkephalin, histamine, OGFR, T-bet, and GATA3 were suppressed by tranexamic acid treatment. Conversely, the levels of ß-endorphin and µ-opioid receptor increased with tranexamic acid treatment. In addition, the expression of the estrogen receptor-ß on the surface of mast cells was increased by tranexamic acid. These results indicate that photoaging induced by UVA eye irradiation can be ameliorated by tranexamic acid through the regulation of hypothalamo-pituitary hormones. Furthermore, this ameliorative effect on photoaging may be due to an increase in estrogen receptor-ß after tranexamic acid treatment.

An Inhibitor of Casein Kinase 1ε/δ (PF670462) Prevents the Deterioration of Dextran Sodium Sulfate-induced Ulcerative Colitis Caused by UVB Eye Irradiation.

Although we previously reported the exacerbation of dextran sodium sulfate (DSS)-induced ulcerative colitis by ultraviolet (UV) B eye irradiation, we do not yet understand the mechanism behind this phenomenon. In this study, we examined the relationship between the deterioration of DSS-induced ulcerative colitis and clock genes. We induced a mouse model of ulcerative colitis by administering DSS for 5 days, and administered UVB eye irradiation on each day of the DSS treatment period. The DSS-induced ulcerative colitis was deteriorated by the UVB eye irradiation. The levels of Clock, brain and muscle arnt-like protein 1 (Bmal1), reverse orientation c-erb A gene (Rev-Erb)α, RAR-related orphan receptor gamma (RORγt), and interleukin (IL)-17 in the colon were increased by UVB eye irradiation in the DSS-treated mice (UVB/DSS-treated mice). Conversely, the nuclear factor, interleukin 3 regulated (NFIL-3) levels in the colon were lower after UVB eye irradiation. The Casein Kinase 1ε/δ inhibitor (PF670462) administration, which is a Clock/Bmal1 inhibitor (PER2 activator), inhibited the deterioration caused by UVB eye irradiation. These results suggest that the UVB eye irradiation-mediated exacerbation of DSS-induced ulcerative colitis depends on IL-17 produced in response to alterations in clock genes.

Ultraviolet B eye irradiation aggravates atopic dermatitis via adrenocorticotropic hormone and NLRP3 inflammasome in NC/Nga mice.

BACKGROUND: Ultraviolet (UV) B irradiation has been shown to improve atopic dermatitis (AD). However, the relationship between UVB eye irradiation and AD is not known. This issue was addressed using a mouse model of AD. METHODS: The eyes of NC/Nga mice were irradiated with UVB at a dose of 1.0 kJ/m2 using a 20SE sunlamp for the duration of the experimental period. RESULTS: AD symptoms deteriorated upon UVB eye irradiation. The levels of adrenocorticotropic hormone (ACTH) in the plasma and nucleotide-binding domain and leucine-rich-containing family, pyrin domain-containing (NLRP)3 and neutrophil markers in the skin were increased in UVB-irradiated mice. Treatment with inhibitors of ACTH, caspase-1, interleukin-18, and thymic stromal lymphopoietin (TSLP) partly reversed the effects of irradiation, with the greatest improvement observed upon ACTH inhibition. The NLRP3 inflammasome was implicated in the effects of UVB irradiation. CONCLUSIONS: UVB eye irradiation causes AD symptom deterioration, which is likely mediated by ACTH and the activity of the inflammasome.

Ultraviolet A Eye Irradiation Ameliorates Atopic Dermatitis via p53 and Clock Gene Proteins in NC/Nga Mice.

Atopic dermatitis (AD) is a widespread chronic skin condition that severely affects quality of life and can lead to more serious complications. Although ultraviolet (UV)A eye irradiation can exert various effects on the skin, it is unknown whether UVA can affect AD. To investigate potential associations, we used an NC/Nga mouse model of AD to study the effects of UVA eye irradiation. The eyes of mice were irradiated with a UVA dose of 100 kJ m-2 using a FL20SBLB-A lamp. Our histological data demonstrated that AD symptoms could be ameliorated by UVA eye irradiation. We also observed an increase in the levels of adrenocorticotropic hormone (ACTH), p53 and retinoid X receptor α (RXRα) in mice with UVA-irradiated eyes. In contrast, the levels of thymic stromal lymphopoietin (TSLP), period 2 (PER2) and differentiated embryo chondrocytes 1 (DEC1) protein were decreased in mice treated with UVA irradiation. Furthermore, UVA eye-irradiated mice exhibited reduced DEC1 and RXRα colocalization compared with nonirradiated mice. These results suggested that p53 and various clock gene proteins played important roles in the amelioration of AD symptoms observed after UVA eye irradiation; this technique may have therapeutic applications in AD.