Yun Sun Lee

Fasting-induced increases of arcuate NPY mRNA and plasma corticosterone are blunted in the rat experienced neonatal maternal separation

This study was conducted to examine the effects of neonatal maternal separation on the hypothalamic expression of feeding peptides in later life. Pups in maternal separation (MS) groups were separated from their dam for 3 h daily from postnatal day (PND) 1-14, while pups in non-handled (NH) groups were left undisturbed. Rats were sacrificed on PND 60 to examine the gene expression of neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in the hypothalamic arcuate nucleus by mRNA in situ hybridization. Half of the rats from each group were food-deprived for 48 h before sacrifice. POMC mRNA expression increased in the free fed MS group compared with the free fed NH group. Food deprivation significantly decreased the arcuate POMC mRNA level in both groups. Body weight gain, basal levels of plasma corticosterone, leptin, and arcuate NPY mRNA were not modulated by experience of neonatal maternal separation. However, fasting-induced increases of plasma corticosterone and arcuate NPY expression were blunted in MS rats. These results suggest that neonatal maternal separation may increase the basal expression level of arcuate POMC mRNA, while inhibit the fasting-induced expression of arcuate NPY mRNA, later in life. Lastly, the altered expression of arcuate NPY mRNA, but not of arcuate POMC mRNA, appeared to be related with altered activity of the hypothalamic-pituitary-adrenal gland axis in offspring by neonatal maternal separation.

DAMP molecules S100A9 and S100A8 activated by IL‐17A and house‐dust mites are increased in atopic dermatitis

S100A9 and S100A8 are called damage‐associated molecular pattern (DAMP) molecules because of their pro‐inflammatory properties. Few studies have evaluated S100A9 and S100A8 function as DAMP molecules in atopic dermatitis (AD). We investigated how house‐dust mites affect S100A9 and S100A8 expression in Th2 cytokine‐ and Th17 cytokine‐treated keratinocytes, and how secretion of these molecules affects keratinocyte‐derived cytokines. Finally, we evaluated expression of these DAMP molecules in AD patients. S100A9 expression and S100A8 expression were strongly induced in IL‐17A‐ and Dermatophagoides (D.) farinae‐treated keratinocytes, respectively. Furthermore, co‐treatment with D. farinae and IL‐17A strongly increased expression of S100A9 and S100A8 compared with D. farinae‐Th2 cytokine co‐treatment. The IL‐33 mRNA level increased in a dose‐dependent manner in S100A9‐treated keratinocytes, but TSLP expression did not change. S100A8/A9 levels were also higher in the lesional skin and serum of AD patients, and correlated with disease severity. Taken together, S100A9 and S100A8 may be involved in inducing DAMP‐mediated inflammation in AD triggered by IL‐17A and house‐dust mites.

Dissemination of ceftazidime-resistant Acinetobacter baumannii clonal complex 92 in Korea

Aims:  This study was performed to describe the epidemiological traits of ceftazidime‐resistant Acinetobacter baumannii clinical isolates from Korea.

Insight into newly discovered innate immune modulation in atopic dermatitis.

Atopic dermatitis (AD) is a highly pruritic, chronic relapsing inflammatory skin disease characterized by innate and adaptive immune reactions. In AD, innate immune mechanisms such as pattern recognition receptors and antimicrobial peptides have been investigated in detail, but recently, epidermis‐derived cytokines, namely thymic stromal lymphopoietin (TSLP), IL‐25 and IL‐33, were shown to participate in innate immune reactions independently of adaptive immunity. In addition to conventional innate cells, such as mast cells, basophils and eosinophils, Th2 cytokine‐producing invariant natural killer T (iNKT) cells, innate lymphoid cells (ILCs) and Th17/Th22 cytokine‐producing innate cells – iNKT cells and natural killer (NK)‐like cells – can participate in innate immune modulation in AD. Accordingly, early control of innate immune responses in AD before activation of adaptive immune responses by conventional T and B cells that perpetuate chronic skin inflammation may adequately alleviate acute exacerbations of AD. Therefore, we hypothesized that select immune modulators targeting the innate immune response could potentially be used for individualized treatment of AD.

Salicylic Acid Peels Versus Jessner’s Solution for Acne Vulgaris: A Comparative Study

BACKGROUND Salicylic acid was recently formulated in a hydroethanolic vehicle at a concentration of 20% to 30%. Salicylic acid has strong comedolytic effects because of its lipophilic nature. OBJECTIVE To compare the therapeutic efficacy and tolerability of salicylic acid peels with those of Jessners solution peels in patients with acne vulgaris. METHODS Thirteen patients (13 men; mean age 22.6, range 20–28) with facial acne were enrolled. Jessners solution was applied to one side of each patients face and 30% salicylic acid to the other in three sessions at 2‐week intervals. A blinded investigator counted noninflammatory and inflammatory lesions before treatment and 2 weeks after each treatment. RESULTS Inflammatory and noninflammatory acne lesion counts decreased in proportion to the duration of treatment. Inflammatory acne lesion counts did not differ significantly between salicylic acid and Jessners solution peels, although in terms of noninflammatory acne lesion counts, sites treated with salicylic acid showed significant improvement (p = .04), whereas those treated with Jessners solution did not. CONCLUSION We found that 30% salicylic acid peels were effective for inflammatory acne and more effective than Jessners solution peels for treating noninflammatory acne.

Knockdown of paraoxonase 1 expression influences the ageing of human dermal microvascular endothelial cells.

Skin is one of the most commonly studied tissues for microcirculation research owing to its close correlation of cutaneous vascular function, ageing and age‐related cardiovascular events. To elucidate proteins that determine this correlation between endothelial cell function and ageing in the vascular environment of the skin, we performed a proteomic analysis of plasma samples from six donors in their 20s (young) and six donors in their 60s (old). Among identified proteins, paraoxonase 1 (PON1) was selected in this study. To elucidate the role of PON1 on skin ageing and determine how it controls cellular senescence, the characteristics of PON1 in human dermal microvascular endothelial cells (HDMECs) were determined. When the expression of endogenous PON1 was knocked‐down by small interfering RNA (siRNA) targeting PON1, HDMECs showed characteristic features of cellular senescence such as increases in senescence‐associated β‐galactosidase stained cells and enlarged and flattened cell morphology. At 48 h post‐transfection, the protein expression of p16 in PON1 siRNA‐treated HDMECs was higher than that in scrambled siRNA‐treated HDMECs. In addition, the expressions of moesin and rho GTP dissociation inhibitor, additional age‐related candidate biomarkers, were decreased by PON1 knock‐down in HDMECs. In conclusion, these results suggest that PON1 functions as an ageing‐related protein and plays an important role in the cellular senescence of HDMECs.

41 S100A8/A9, a Damp Molecule Activated by IL-17 and House Dust Mite is Upregulated in Atopic Dermatitis.

Background S100A8/A9 (Calgranulin A/B, Calprotectin), a heterodimer of 2 calcium-binding proteins originally found in the cytoplasm of neutrophils and membrane of monocytes. It has emerged as an important pro-inflammatory mediator, so called “damage-associated molecular pattern (DAMP)” molecule in acute and chronic inflammation. Our previous proteomics data showed that S100A8/A9 was significantly downregulated after immunotherapy with house dust mite in patients with atopic dermatitis (AD). Methods The purpose of this study was to evaluate S100A8/A9 expression in serum and lesional skin of AD patients, and then to assess S100A8/A9 expression in HaCaT cells and primary human keratinocytes, which were cultured with Th2, Th17 cytokines and house dust mite (HDM) extracts. Results Compared with healthy controls, serum S100A8/A9 levels were higher in AD patients and correlated with eczema area and severity index (EASI) scores (P < 0.01, r2 = 0.2037). S100A8/A9 was strongly expressed in the upper epidermis of AD tissues by immunofluorescence. IL-17A strongly induced S100A8/A9, and enhanced S100A8/A9 expression in HaCaT cells and human keratinocytes which were cultured with Th2 cytokines. S100A8/A9 mRNA and protein levels were also increased in HaCaT cells and human keratinocytes which were stimulated with Dermatophagoides farinae by time dependent manner. IL-17A also strongly enhanced S100A8/A9 expression in HaCaT cells which were cultured with D. farinae, but Th2 cytokines did not. Conclusions These results suggest that elevated S100A8/A9 levels of AD patients may reflect the importance of DAMP-associated inflammation, which could be triggered by Th17 cytokines and HDM allergens in AD.