Psoriasis is a chronic inflammatory skin disease. Recently, lysophosphatidic acid (LPA)/LPAR5 signaling has been reported to be involved in both NLRP3 inflammasome activation in macrophages and ...keratinocyte activation to produce inflammatory cytokines, contributing to psoriasis pathogenesis. However, the effect and molecular mechanisms of LPA/LPAR signaling in keratinocyte proliferation in psoriasis remain unclear. In this study, we investigated the effects of LPAR1/3 inhibition on imiquimod (IMQ)-induced psoriasis-like mice. Treatment with the LPAR1/3 antagonist, ki16425, alleviated skin symptoms in IMQ-induced psoriasis-like mouse models and decreased keratinocyte proliferation in the lesion. It also decreased LPA-induced cell proliferation and cell cycle progression via increased cyclin A2, cyclin D1, cyclin-dependent kinase (CDK)2, and CDK4 expression and decreased p27Kip1 expression in HaCaT cells. LPAR1 knockdown in HaCaT cells reduced LPA-induced proliferation, suppressed cyclin A2 and CDK2 expression, and restored p27Kip1 expression. LPA increased Rho-associated protein kinase 2 (ROCK2) expression and PI3K/AKT activation; moreover, the pharmacological inhibition of ROCK2 and PI3K/AKT signaling suppressed LPA-induced cell cycle progression. In conclusion, we demonstrated that LPAR1/3 antagonist alleviates IMQ-induced psoriasis-like symptoms in mice, and in particular, LPAR1 signaling is involved in cell cycle progression via ROCK2/PI3K/AKT pathways in keratinocytes.
Recent evidence of gut microbiota dysbiosis in the context of psoriasis and the increased cooccurrence of inflammatory bowel disease and psoriasis suggest a close relationship between skin and gut ...immune responses. Using a mouse model of psoriasis induced by the Toll-like receptor (TLR) 7 ligand imiquimod, we found that psoriatic dermatitis was accompanied by inflammatory changes in the small intestine associated with eosinophil degranulation, which impaired intestinal barrier integrity. Inflammatory responses in the skin and small intestine were increased in mice prone to eosinophil degranulation. Caco-2 human intestinal epithelial cells were treated with media containing eosinophil granule proteins and exhibited signs of inflammation and damage. Imiquimod-induced skin and intestinal changes were attenuated in eosinophil-deficient mice, and this attenuation was counteracted by the transfer of eosinophils. Imiquimod levels and the distribution of eosinophils were positively correlated in the intestine. TLR7-deficient mice did not exhibit intestinal eosinophil degranulation but did exhibit attenuated inflammation in the skin and small intestine following imiquimod administration. These results suggest that TLR7-dependent bidirectional skin-to-gut communication occurs in psoriatic inflammation and that inflammatory changes in the intestine can accelerate psoriasis.
Previous studies have reported numerous environmental factors for atopic dermatitis (AD), such as allergens and chemical stimulants. However, few studies have addressed the relationship between ...ambient air pollution and AD at a population level.
To evaluate the effect of air pollutants on medical care visits for AD and to identify susceptible populations.
In this time-series study conducted on 513,870 medical care visits for AD from 2012 to 2015 identified by reviewing national health insurance claim data in Incheon, Republic of Korea. Treating daily number of medical care visits for AD as a dependent variable, generalized additive models with Poisson distributions were constructed, which included air pollutant levels, ambient temperature, relative humidity, day of the week, national holiday, and season. Risks were expressed as relative risks (RR) with 95% confidence intervals (95% CIs) per interquartile range increase of each air pollutant.
Higher levels of particulate matter of diameter ≤10 μm (PM10) (RR, 1.009; 95% CI, 1.007–1.012), ozone (1.028; 1.023–1.033), and sulfur dioxide (1.033; 1.030–1.037) were significantly associated with increased risk of medical care visits for AD on same days. In all age and sex groups, ozone was associated with a significantly higher risk of medical care visits, with the greatest risk among 13- to 18-year-old males (RR, 1.127; 95% CI, 1.095–1.159).
This study suggests relationships of ambient PM10, ozone, and sulfur dioxide levels with medical care visits for AD.
In this 4-year time-series study, we used national medical claims data that reasonably represented the Korean population to address the relationship between ambient air pollution and atopic dermatitis at a population level. The study conducted on 513,870 medical care visits for AD from 2012 to 2015 identified by reviewing national health insurance claim data in Incheon, Republic of Korea.We found atmospheric PM10, O3, and SO2 levels were positively associated with medical care visits for AD. A history of AD had an interactive effect on the risk of medical care visits for AD associated with either O3 or SO2. Children and adolescents aged <19 years and those without a history of AD or allergic rhinitis were found to be susceptible populations.
Purpose
The purpose of this study was to compare cutaneous heat pain thresholds using the method of limit and level.
Methods
Sixteen young males (23.2 ± 3.2 year, 174.9 ± 4.9 cm, and 70.1 ± 8.6 kg) ...participated in this study. The thermode temperature increased at a constant rate of 0.1 °C s
−1
from 33 °C for the method of limit, whereas the method of level consisted of 3 s heat pulses increasing from 44 °C to 50 °C in 100 s separated by 5 s intervals. All measurements were conducted on 14 body regions (the forehead, neck, chest, abdomen, upper back, upper arm, forearm, waist, hand, palm, thigh, calf, foot, and sole) in 28 °C, 35% relative humidity.
Results
The results are as follows. Heat pain thresholds were on average 3.2 ± 2.1 °C higher for the method of level than for the method of limit (
P
< 0.05). Second, the correlation coefficient between values by two methods was 0.819 (
P
< 0.01). Third, lower body regions (thigh, calf, and sole) had higher heat pain thresholds than upper body regions (chest) by the method of level only (
P
< 0.05). Fourth, body regional subcutaneous fat thickness showed no relationship with heat pain thresholds except the upper arm.
Conclusion
These results indicated that cutaneous heat pain thresholds vary based on the type of heat stimuli and body regions. The method of limit could be applied for predicting accumulated thermal pain starting from moderate heat, whereas the method of level may be applicable for predicting acute heat pain to flames or high heat.
Stem cells introduced to site of injury primarily act via indirect paracrine effects rather than direct cell replacement of damaged cells. This gives rise to understanding the stem cell secretome. In ...this study, in vitro studies demonstrate that the secretome activates the PI3K/Akt or FAK/ERK1/2 signaling cascades and subsequently enhances the proliferative and migratory abilities of various types of skin cells, such as fibroblasts, keratinocytes, and vascular epithelial cells, ultimately accelerating wound contraction. Indeed, inhibition of these signaling pathways with synthetic inhibitors resulted in the disruption of secretome-induced beneficial effects on various skin cells. In addition, major components of the stem cell secretome (EGF, basic FGF, and HGF) may be responsible for the acceleration of wound contraction. Stimulatory effects of these three prominent factors on wound contraction are achieved through the upregulation of PI3K/Akt or FAK/ERK1/2 activity. Overall, we lay the rationale for using the stem cell secretome in promoting wound contraction. In vivo wound healing studies are warranted to test the significance of our in vitro findings.
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The stem cell secretome, which contains various growth factors, especially EGF, bFGF, and HGF, accelerates wound healing by stimulating the proliferative and migratory abilities of existing skin cells through multiple signaling pathways. The stem cell secretome might therefore be a promising alternative for the treatment of cutaneous wounds.
Accumulating data have indicated a fundamental role of eosinophils in regulating adipose tissue homeostasis. Here, we performed whole-genome RNA sequencing of the small intestinal tract, which ...suggested the presence of impaired lipid metabolism in eosinophil-deficient ΔdblGATA mice. ΔdblGATA mice fed a high-fat diet (HFD) showed reduced body fat mass, impaired enlargement of adipocytes, decreased expression of adipogenic genes, and developed glucose intolerance. HFD induced accumulation of eosinophils in the perigonadal white adipose tissue. Concordantly, adipocyte-differentiated 3T3-L1 cells promoted the migration of eosinophils through the expression of CCL11 (eotaxin-1) and likely promoted their survival through the expression of interleukin (IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor. HFD-fed ΔdblGATA mice showed increased infiltration of macrophages, CD4
T-cells, and B-cells, increased expression of interferon-γ, and decreased expression of IL-4 and IL-13 in white adipose tissue. Interferon-γ treatment significantly decreased lipid deposition in adipocyte-differentiated 3T3-L1 cells, while IL-4 treatment promoted lipid accumulation. Notably, HFD-fed ΔdblGATA mice showed increased lipid storage in the liver as compared with wild-type mice. We propose that obesity promotes the infiltration of eosinophils into adipose tissue that subsequently contribute to the metabolic homeostasis by promoting adipocyte maturation.
This descriptive study was aimed to examine trends in the incidence of melanoma and nonmelanoma in South Korea.
The nationwide incidence data for melanoma and non-melanoma skin cancer was obtained ...from the Korea Central Cancer Registry. Age-standardized rates were calculated and analyzed, using a Joinpoint regression model.
The incidence of basal cell carcinoma has increased dramatically both in men (average annual percentage change AAPC, 8.0 95% confidence interval (CI), 6.0 to 10.1) and women (AAPC, 9.0 95% CI, 7.5 to 10.4). Squamous cell carcinoma has also steadily increased both in men (AAPC, 3.3 95% CI, 2.6 to 4.0) and women (AAPC, 6.8 95% CI, 5.3 to 8.4). Cutaneous melanoma increased continuously from 1999 to 2014 inwomen (AAPC, 3.5 95% CI, 2.4 to 4.6), whilst rapidly increasing in men until 2005 (APC, 7.9 95% CI, 2.4 to 13.7) after which no increase has been observed (APC, ‒0.2 95% CI, ‒2.3 to 2.0).
The incidence rates of melanoma and non-melanoma skin cancer have increased over the past years, with the exception of melanoma in men. Further studies are required to investigate the reasons for the increased incidence of these skin cancers in South Korea.
Atopic dermatitis is a chronic skin inflammatory disease mediated by Th2-type immune responses. Although intestinal immune responses have been shown to play a critical role in the development or ...prevention of atopic dermatitis, the precise influence of intestinal immunity on atopic dermatitis is incompletely understood. We show here that orally tolerized mice are protected from experimental atopic dermatitis induced by sensitization and epicutaneous (EC) challenge to ovalbumin. Although the expression of Th2-type cytokines in the small intestine of orally tolerized and EC-challenged mice did not change significantly, these mice showed decreased inflammatory responses in the small intestine with restoration of microbial change elicited by the EC challenge. Interestingly, an increase in small intestinal eosinophils was observed with the EC challenge, which was also inhibited by oral tolerance. The role of small intestinal eosinophils and microbiota in the pathogenesis of experimental atopic dermatitis was further substantiated by decreased inflammatory mediators in the small intestine and attenuated Th2-type inflammation in the skin of eosinophil-deficient and microbiota-ablated mice with EC challenges. Based on these data, we propose that the bidirectional interaction between the skin and the intestine has a role in the pathogenesis of atopic dermatitis and that modulation of the intestinal microenvironments could be a therapeutic approach to atopic dermatitis.
Although previous studies suggest that previous pulmonary tuberculosis was associated with increased risk of lung cancer. It remains controversial whether pulmonary tuberculosis is a risk factor for ...lung cancer. Our study was aimed to examine the association between pulmonary tuberculosis and lung cancer risk in Korean.
The Korean National Health and Nutrition Examination Survey database was linked with the Korean National Cancer Incidence Database to examine the occurrence of pulmonary tuberculosis and lung cancer. The linked databases were also merged with causes of death database of Statistics Korea. The Cox-proportional hazards model was used to estimates the hazard risk of lung cancer for Korean adults aged ≥40 years with pulmonary tuberculosis.
Of 20,252 total participants, 2,640 (13.0%) had old pulmonary tuberculosis (a medical history of pulmonary tuberculosis or radiologically inactive tuberculosis). After adjusting for all covariates, the hazard ratio of lung cancer among patients with old pulmonary tuberculosis was 3.24 (95% CI, 1.87‒5.62) compared to the control group. According to smoking status, the hazard ratios of lung cancer for never smokers, ex-smokers, and current smokers among participants with old pulmonary tuberculosis were 3.52 (95% CI, 1.17‒10.63), 2.16 (95% CI, 0.89‒5.24), and 3.71 (95% CI, 1.49‒9.22) compared to the control group, respectively.
Korean adults with old pulmonary tuberculosis have a higher risk of lung cancer, compared to general population without pulmonary tuberculosis.
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