Intracellular 3′,5′-Adenosine Cyclic Monophosphate Level Regulates House Dust Mite-Induced Interleukin-13 Production by T Cells from Mite-Sensitive Patients with Atopic Dermatitis

We studied the relationship between cAMP and house dust mite-induced cytokine production in T cells from mite-sensitive patients with atopic dermatitis. T cells from atopic dermatitis patients secreted high level of interleukin-13 (mean 851.1 pg per ml) when cultured with autologous monocytes pulsed with Dermatophagoides pteronyssinus extract. Dermato- phagoides pteronyssinus-induced interleukin-13 secretion was not detected in normal subjects. Adenylate cyclase inhibitor MDL 12,330A and cyclic nucleotide phosphodiesterase type 4 inhibitor rolipram blocked Dermatophagoides pteronyssinus-induced interleukin-13 secretion in atopic dermatitis T cells. In atopic dermatitis T cells, cAMP level rose at 5 min after Dermatophagoides pteronyssinus stimulus then decreased to the basal level at 1 h. MDL 12,330A blocked the Dermatophagoides pteronyssinus-induced cAMP elevation while rolipram blocked its reversal. In atopic dermatitis T cells, adenylate cyclase activity increased at 5 min after Dermatophagoides pteronyssinus stimulus, followed by the increase of cyclic nucleotide phosphodiesterase acvity at 15 min. In atopic dermatitis T cells, phospholipase C inhibitor ET-18-OCH3 blocked Dermatophagoides pteronyssinus-induced activation of adenylate cyclase, while rolipram, protein kinase A inhibitor H-89, and MDL 12,330A blocked the activation of cyclic nucleotide phosphodiesterase. These results suggest that Dermatophagoides pteronyssinus may first increase cAMP in atopic dermatitis T cells by activating adenylate cyclase via phospholipase C, and next decrease cAMP by activating cyclic nucleotide phosphodiesterase 4 via protein kinase A, which may be activated by adenylate cyclase-generated cAMP signal. These events are required for interleukin-13 response Dermatophagoides pteronyssinus

17β-Estradiol Enhances the Production of Nerve Growth Factor in THP-1-Derived Macrophages or Peripheral Blood Monocyte-Derived Macrophages

We examined in vitro effects of 17β-estradiol (E2) on nerve growth factor production by macrophages derived from monocytic cell line THP-1-or periphereal blood monocytes. E2 and membrane-impermeable bovine serum albumin-conjugated E2 (E2-BSA) enhanced nerve growth factor secretion and mRNA expression in both types of macrophages E2 enhanced nerve growth factor promotor activity in THP-1-derived macrophages and two activator protein-1 binding sites on the promoter were responsible for the enhancement. E2 and E2-BSA enhanced transcriptional activity and DNA binding of activator protein-1. E2 and E2-BSA shifted the activator protein-1 composition from c-Jun homodimers to c-Fos/c-Jun heterodimers. E2 and E2-BSA transiently induced c-Fos mRNA, which was constitutively undetectable in both types of macrophages. Adenylate cyclase inhibitor SQ22536 suppressed E2-induced nerve growth factor production and c-Fos expression. E2 and E2-BSA increased intracellular cyclic adenosine monophosphate level in both types of macrophages. Antisense oligonucleotide against guanine nucleotide-binding protein-coupled receptor, GPR30 suppressed the E2-induced cyclic adenosine monophosphate signal, c-Fos expression, and nerve growth factor secretion in both types of macrophages. These results suggest that E2 may enhance nerve growth factor production by inducing c-Fos expression via cyclic adenosine monophosphate signal in macrophages. These effects may be mediated via GPR30

17β-estradiol Inhibits the Production of RANTES in Human Keratinocytes

A chemokine, regulated upon activation, normal T cell expressed and secreted (RANTES) attracts T helper-1 cells and macrophages. The production of RANTES is enhanced in keratinocytes of psoriatic skin lesions, which may contribute to the inflammatory infiltrate. It is known that estrogen regulates the natural course of psoriasis. We examined the in vitro effects of 17β-estradiol on RANTES production by human keratinocytes. 17β-estradiol inhibited tumor necrosis factor-α or interleukin-1β-induced RANTES secretion, mRNA expression, and promoter activity in keratinocytes, and these effects of 17β-estradiol were counteracted by estrogen receptor antagonist ICI 182 780. Two nuclear factor κB elements on RANTES promoter were required for tumor necrosis factor-α or interleukin-1β-induced transcription and involved in the inhibition by 17β-estradiol. 17β-estradiol inhibited nuclear factor κB transcriptional activity, whereas it did not inhibit DNA binding of nuclear factor κB or phosphorylation or degradation of the inhibitor of nuclear factor κB α in tumor necrosis factor-α or interleukin-1β-stimulated keratinocytes. 17β-estradiol-induced inhibition of nuclear factor κB transcriptional activity and RANTES promoter activity was rescued by overexpression of a coactivator cyclic AMP response element-binding protein (CREB) or nuclear factor κB p65 but not by steroid receptor coactivator-1 or nuclear factor κB p50. The overexpression of CREB-binding protein rescued 17β-estradiol-induced inhibition of transcription mediated by a chimeric protein, GAL4-p65286–551, which contained GAL4 DNA binding domain fused to C-terminal transactivating domain of p65 (amino acids 286–551). The transfection of estrogen receptor α or estrogen receptor β into estrogen receptor-negative SKBR3 cells resulted in 17β-estradiol-mediated inhibition of transcription via GAL4-p65286–551. These results suggest that 17β-estradiol-bound estrogen receptor may inhibit nuclear factor κB-dependent transcription of RANTES gene by competing with p65 for limiting amounts of CREB-binding protein

Simulation of Electrical and Thermal Properties of Granite under the Application of Electrical Pulses Using Equivalent Circuit Models

Since energy efficiency in comminution of ores is as small as 1% using a mechanical crushing process, it is highly demanded to improve its efficiency. Using electrical impulses to selectively liberate valuable minerals from ores can be a solution of this problem. In this work, we developed a simulation method using equivalent circuits of granite to better understand the crushing process with high-voltage (HV) electrical pulses. From our simulation works, we calculated the electric field distributions in granite when an electrical pulse was applied. We also calculated other associated electrical phenomena such as produced heat and temperature changes from the simulation results. A decrease in the electric field was observed in the plagioclase with high electrical conductivity and void space. This suggests that the void volume in each mineral is important in calculating the electrical properties. Our equivalent circuit models considering both the electrical conductivity and dielectric constant of a granite can more accurately represent the electrical properties of granite under HV electric pulse application. These results will help us better understand the liberation of minerals from granite by electric pulse application

Equivalent Circuit Models: An Effective Tool to Simulate Electric/Dielectric Properties of Ores-An Example Using Granite

The equivalent circuit model is widely used in high-voltage (HV) engineering to simulate the behavior of HV applications for insulation/dielectric materials. In this study, equivalent circuit models were prepared in order to represent the electric and dielectric properties of minerals and voids in a granite rock sample. The HV electric-pulse application shows a good possibility of achieving a high energy efficiency with the size reduction and selective liberation of minerals from rocks. The electric and dielectric properties were first measured, and the mineral compositions were also determined by using a micro-X-ray fluorescence spectrometer. Ten patterns of equivalent circuit models were then prepared after considering the mineral distribution in granite. Hard rocks, as well as minerals, are dielectric materials that can be represented as resistors and capacitors in parallel connections. The values of the electric circuit parameters were determined from the known electric and dielectric parameters of the minerals in granite. The average calculated data of the electric properties of granite agreed with the measured data. The conductivity values were 53.5 pS/m (measurement) and 36.2 pS/m (simulation) in this work. Although there were some differences between the measured and calculated data of dielectric loss (tan delta), their trend as a function of frequency agreed. Even though our study specifically dealt with granite, the developed equivalent circuit model can be applied to any other rock