Solution-processable low-voltage carbon nanotube field-effect transistors with high-krelaxor ferroelectric polymer gate insulator.

Achieving energy-efficient and high-performance field-effect transistors (FETs) is one of the most important goals for future electronic devices. This paper reports semiconducting single-walled carbon nanotube FETs (s-SWNT-FETs) with an optimized high-krelaxor ferroelectric insulator P(VDF-TrFE-CFE) thickness for low-voltage operation. The s-SWNT-FETs with an optimized thickness (∼800 nm) of the high-kinsulator exhibited the highest average mobility of 14.4 cm2V-1s-1at the drain voltage (ID) of 1 V, with a high current on/off ratio (Ion/off>105). The optimized device performance resulted from the suppressed gate leakage current (IG) and a sufficiently large capacitance (>50 nF cm-2) of the insulating layer. Despite the extremely high capacitance (>100 nF cm-2) of the insulating layer, an insufficient thickness (<450 nm) induces a highIG, leading to reducedIDand mobility of s-SWNT-FETs. Conversely, an overly thick insulator (>1200 nm) cannot introduce sufficient capacitance, resulting in limited device performance. The large capacitance and sufficient breakdown voltage of the insulating layer with an appropriate thickness significantly improved p-type performance. However, a reduced n-type performance was observed owing to the increased electron trap density caused by fluorine proportional to the insulator thickness. Hence, precise control of the insulator thickness is crucial for achieving low-voltage operation with enhanced s-SWNT-FET performance.

TSLP up-regulates inflammatory responses through induction of autophagy in T cells.

Thymic stromal lymphopoietin (TSLP), a type I cytokine belonging to the IL-2 cytokine family, promotes Th2-mediated inflammatory responses. The aim of this study is to investigate whether TSLP increases inflammatory responses via induction of autophagy using a murine T cell lymphoma cell line, EL4 cells, and lipopolysaccharide (LPS)-injected mice. TSLP increased expression levels of autophagy-related factors, such as Beclin-1, LC3-II, p62, Atg5, and lysosome associated membrane protein 1/2, whereas these factors increased by TSLP disappeared by neutralization of TSLP in EL4 cells. TSLP activated JAK1/JAK2/STAT5/JNK/PI3K, while the blockade of JAK1/JAK2/STAT5/JNK/PI3K signaling pathways reduced the expression levels of Beclin-1, LC3-II, and p62 in TSLP-stimulated EL4 cells. In addition, TSLP simultaneously increased levels of inflammatory cytokines via induction of autophagy by activation of JAK1/JAK2/STAT5/JNK/PI3K signaling pathways. In an LPS-induced acute liver injury (ALI) mouse model, exogenous TSLP increased expression levels of Beclin-1 and LC3-II, whereas functional deficiency of TSLP by TSLP siRNA resulted in lower expression of Beclin-1, LC3-II, and inflammatory cytokines, impairing their ability to form autophagosomes in ALI mice. Thus, our findings show a new role of TSLP between autophagy and inflammatory responses. In conclusion, regulating TSLP-induced autophagy may be a potential therapeutic strategy for inflammatory responses.

Correction: Han et al. Dexamethasone Attenuates Oncostatin M Production via Suppressing of PI3K/Akt/NF-κB Signaling in Neutrophil-like Differentiated HL-60 Cells. Molecules 2022, 27, 129.

In the original article [...].

Resveratrol Downregulates Granulocyte-Macrophage Colony-Stimulating Factor-Induced Oncostatin M Production through Blocking of PI3K/Akt/NF-κB Signal Cascade in Neutrophil-like Differentiated HL-60 Cells.

Oncostatin M (OSM) is essential in a wide range of inflammatory responses, and most OSM is produced by neutrophils in respiratory diseases. While resveratrol (RES) is regarded as an anti-inflammatory agent in a variety of conditions, the mechanism of OSM inhibition by RES in neutrophils remains to be elucidated. In this study, we investigated whether RES could inhibit OSM production in neutrophil-like differentiated (d)HL-60 cells. The effects of RES were measured by means of an enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Increases in production and mRNA expression of OSM resulted from the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) in neutrophil-like dHL-60 cells; however, these increases were downregulated by RES treatment. Exposure to GM-CSF led to elevations of phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, and nuclear factor (NF)-kB. Treatment with RES induced downregulation of the phosphorylated levels of PI3K, Akt, and NF-κB in neutrophil-like dHL-60 cells. These results suggest that RES could be applicable to prevent and/or treat inflammatory disorders through blockade of OSM.

Dexamethasone Attenuates Oncostatin M Production via Suppressing of PI3K/Akt/NF-κB Signaling in Neutrophil-like Differentiated HL-60 Cells.

Oncostatin M (OSM) plays a role in various inflammatory reactions, and neutrophils are the main source of OSM in pulmonary diseases. However, there is no evidence showing the mechanism of OSM production in neutrophils. While dexamethasone (Dex) has been known to exert anti-inflammatory activity in various fields, the precise mechanisms of OSM downregulation by Dex in neutrophils remain to be determined. Here, we examined how OSM is produced in neutrophil-like differentiated HL-60 cells. Enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot analysis were utilized to assess the potential of Dex. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation resulted in OSM elevation in neutrophil-like dHL-60 cells. OSM elevation induced by GM-CSF is regulated by phosphatidylinositol 3-kinase (PI3K)/Akt/nuclear factor (NF)-kB signal cascades. GM-CSF stimulation upregulated phosphorylated levels of PI3K or Akt or NF-κB in neutrophil-like dHL-60 cells. Treatment with Dex decreased OSM levels as well as the phosphorylated levels of PI3K or Akt or NF-κB in neutrophil-like dHL-60 cells. Our findings show the potential of Dex in the treatment of inflammatory diseases via blocking of OSM.

Efficient production process of bioactive recombinant human leukemia inhibitory factor in Chinese hamster ovary cells.

The rhLIF is widely used as an essential factor in stem cell cultures for cell therapies. However, all the recombinant LIFs commercially available are expensive, and no commercially available rhLIF meet the standards recommended by USP for use in cell therapies. The current study reports the efficient production of N-glycosylated and bioactive rhLIF in CHO cells. The production rate of established rhLIF-expressing rCHO cells was approximately 0.85 g/l in 12-day fed-batch cultures using a 7.5 l bioreactor. The rhLIF protein was purified via a four-step purification procedure with approximately 57% recovery rate and greater than 99% purity. The purified rhLIF was N-glycosylated and biologically active with an EC50 of 0.167 ng/ml and a specific activity of 0.86 × 103 IU/mg. The purification procedure controlled the levels of process-related impurities below critical levels recommended by USP for cytokines used in cell therapies. The current work is the first production process of N-glycosylated and bioactive rhLIF, which can be applied to large-scale manufacture of GMP-grade rhLIF for use as an ancillary material in cell therapy.

Effects of Resveratrol on Thymic Stromal Lymphopoietin Expression in Mast Cells.

Background and objectives: Cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathogenesis of atopic diseases such as atopic dermatitis, allergic rhinitis, and asthma. Resveratrol (RSV) exerts various pharmacological effects such as antioxidant, anti-inflammatory, neuroprotective, and anticancer. Although, it has been verified the beneficial effects of RSV on various subjects, the effect of RSV on thymic stromal lymphopoietin (TSLP) regulation has not been elucidated. Materials and Methods: Here, we examined how RSV regulates TSLP in HMC-1 cells. Enzyme-linked immunosorbent assay, real-time polymerase chain reaction, Western blotting, and calcium assay were performed to evaluate the effect of RSV. Results: TSLP production and mRNA expression were reduced by RSV. RSV down-regulated nuclear factor-κB activation, IκBα phosphorylation as well as activation of receptor-interacting protein2 and caspase-1 in HMC-1 cells. In addition, RSV treatment decreased the up-regulation of intracellular calcium in HMC-1 cells. Conclusions: These results suggest that RSV might be useful for the treatment of atopic diseases through blocking of TSLP.

Chrysophanol, an anthraquinone from AST2017-01, possesses the anti-proliferative effect through increasing p53 protein levels in human mast cells.

OBJECTIVE: Natural products are well known as the source of drugs in the treatment of allergic inflammation. Chrysophanol, an anthraquinone from the AST2017-01 extract, showed a beneficial anti-inflammatory effect on activated human mast cells in our previous study. However, a regulatory effect of AST2017-01 and chrysophanol on mast cell proliferation induced by thymic stromal lymphopoietin (TSLP) remains unclear. The present study determined the anti-proliferative effect and the fundamental mechanism of AST2017-01 and chrysophanol in mast cells. METHODS: We evaluated an anti-proliferative effect of AST2017-01 and chrysophanol in TSLP-stimulated human mast cell line, HMC-1. RESULTS: Without cytotoxicity, AST2017-01 and chrysophanol decreased mast cells growth and Ki67 mRNA expression increased by TSLP. AST2017-01 and chrysophanol enhanced expressions of p53 and Bax, whereas inhibited expression of Bcl-2. AST2017-01 and chrysophanol restored caspase-3 activity which was decreased by TSLP. AST2017-01 and chrysophanol suppressed expressions of murine double minute-2 protein and phosphorylated-signal transducer and activator of transcription six which are associated with the regulation of p53 protein. AST2017-01 and chrysophanol decreased levels of interleukin (IL)-13, IL-6, and tumor necrosis factor-α. Moreover, AST2017-01 and chrysophanol reduced mRNA expressions of TSLP receptor and IL-7 receptor α. CONCLUSIONS: Therefore, this study proposes that AST2017-01 and chrysophanol may be promising candidates for the development of potent anti-inflammatory or health functional foods.

Use of Physcion to Improve Atopic Dermatitis-Like Skin Lesions through Blocking of Thymic Stromal Lymphopoietin.

Physcion is well known for the treatment of carcinoma. However, the therapeutic effect of physcion on atopic dermatitis (AD) through the inhibition of thymic stromal lymphopoietin (TSLP) level remains largely unknown. In this study, we investigated the anti-AD effect of physcion using HMC-1 cells, splenocytes, and a murine model. Treatment with physcion decreased production and mRNA expression levels of TSLP, IL-6, TNF-ɑ, and IL-1ß in activated HMC-1 cells. Physcion reduced the expression levels of RIP2/caspase-1 and phospho (p)ERK/pJNK/pp38 in activated HMC-1 cells. Physcion suppressed the expression levels of pIKKß/NF-κB/pIkB in activated HMC-1 cells. Moreover, physcion attenuated the production levels of TSLP, IL-4, IL-6, TNF-, and IFN-γ from activated splenocytes. Oral administration of physcion improved the severity of 2,4-dinitrochlorobenzene-induced AD-like lesional skin through reducing infiltration of inflammatory cells and mast cells, and the protein and mRNA levels of TSLP, IL-4, and IL-6 in the lesional skin tissues. Physcion attenuated histamine, IgE, TSLP, IL-4, IL-6, and TNF- levels in serum. In addition, physcion inhibited caspase-1 activation in the lesional skin tissues. These findings indicate that physcion could ameliorate AD-like skin lesions by inhibiting TSLP levels via caspase-1/MAPKs/NF-kB signalings, which would provide experimental evidence of the therapeutic potential of physcion for AD.

Inhibitory effect of naringenin via IL-13 level regulation on thymic stromal lymphopoietin-induced inflammatory reactions.

Naringenin (NG) has various beneficial properties, such as anti-cancer and anti-inflammatory effects. Thymic stromal lymphopoietin (TSLP) induces mast cell proliferation and inflammatory reactions. The aim of this study was to investigate the regulatory effect of NG on TSLP-induced mast cell proliferation and inflammatory reactions using human mast cell line (HMC-1) cells. HMC-1 cells were pre-treated with NG and then treated with TSLP. HMC-1 cells proliferation was determined by quantifying bromodeoxyuridine incorporation. Levels of anti-apoptotic and pro-apoptotic factors were analyzed by western blot analysis. The productions and mRNA expressions of interleukin (IL)-13 and tumour necrosis factor-α (TNF-α) were analyzed by ELISA and quantitative real-time PCR. We found that NG significantly attenuated HMC-1 cells proliferation and Ki-67 mRNA expression promoted by TSLP. NG significantly suppressed mRNA expression of TSLP receptor and IL-7 receptor α in TSLP-treated HMC-1 cells. NG significantly down-regulated levels of phosphorylated-signal transducer and activation of transcription 6 and murine double-minute 2 in TSLP-treated HMC-1 cells, up-regulated levels of cleaved poly ADP-ribose polymerase and p53 in TSLP-treated HMC-1 cells. Furthermore, NG significantly decreased the productions and mRNA expressions of IL-13 and TNF-α in TSLP-treated HMC-1 cells. These results suggest NG has an inhibitory effect on mast cell-mediated allergic inflammatory reactions.

Cordycepin ameliorates skin inflammation in a DNFB-challenged murine model of atopic dermatitis.

OBJECTIVES: Atopic dermatitis (AD) is an allergic and inflammatory skin disorder caused by a combination of itching and skin sensitization by allergens. This article investigated whether cordycepin modulates AD symptoms by using an AD murine model. MATERIAL AND METHODS: We evaluated a regulatory effect and specific molecular mechanism of cordycepin on AD induced by the repeated local exposure of 2,4-dinitrochlorobenzene to dorsal skin of mice. Blood or AD-like skin lesions samples were removed for histopathologic analysis, enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blot analyses. RESULTS: Oral administration of cordycepin decreased duration of scratching behavior and serum levels of histamine and immunoglobulin E increased by DNFB challenge. Cordycepin attenuated clinical symptoms and epidermis thickness of AD mice. In addition, cordycepin reduced thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-6, and tumor necrosis factor-α levels in the serum of AD mice. Cordycepin-attenuated infiltrations of mast cells and eosinophils with decreases in TSLP, macrophage inflammatory protein-2, and intercellular adhesion molecule-1 protein levels in AD-like skin lesions. Messenger RNA expressions of TSLP, thymus and activation-regulated chemokine/CCL17, and C-C chemokine receptor type 3 in AD-like skin lesions were also suppressed by cordycepin. Cordycepin inhibited caspase-1 expressions and activities in AD-like skin lesions. CONCLUSIONS: In conclusion, this study demonstrates that cordycepin ameliorates AD symptoms, suggesting that cordycepin might be a candidate to treat allergic skin diseases.

Anti-inflammatory effects of Artemisia scoparia and its active constituent, 3,5-dicaffeoyl-epi-quinic acid against activated mast cells.

OBJECTIVES: Artemisia scoparia Waldst. et Kit. (AS) has been used to treat inflammation, urticaria and hepatitis. However, the scientific studies of AS and its active compound for inflammatory reactions in activated human mast cell line, HMC-1 cells have not yet been elucidated. MATERIALS AND METHODS: Here, we isolated 3,5-dicaffeoyl-epi-quinic acid (DEQA) from AS butanol fraction. The anti-inflammatory effect of AS and its new active compound, DEQA was examined in HMC-1 cells by studying the following markers: phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced thymic stromal lymphopoietin (TSLP), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 secretion and mRNA expression by ELISA and RT-PCR, respectively. Furthermore, mechanism related to anti-inflammatory was examined by Western blotting. RESULTS: We reported that AS and its new active compound, DEQA significantly reduced TSLP, TNF-α, IL-1ß and IL-6 production levels through the reduction of caspase-1 activity. The mRNA expression of these inflammatory cytokine was also reduced via blocking nuclear factor-κB nuclear translocation by AS and DEQA. In addition, AS significantly reduced phosphorylated-c-Jun N-terminal kinase level and DEQA significantly reduced both phosphorylated-c-Jun N-terminal kinase and -p38 mitogen-activated protein kinase levels. CONCLUSIONS: Therefore, these results indicated that AS and its active compound, DEQA may improve mast cell-mediated inflammatory diseases.

Effects of Linalyl Acetate on Thymic Stromal Lymphopoietin Production in Mast Cells.

Thymic stromal lymphopoietin (TSLP) is an important factor responsible for the pathogenesis of allergic diseases, such as atopic dermatitis and asthma. Because linalyl acetate (LA) possesses a wide range of pharmacological properties, being antispasmodic, anti-inflammatory, and anti-hyperpigmentation, we hypothesized that LA could inhibit TSLP. Therefore, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, caspase-1 assay, Western blot analysis, fluorescent analyses of the intracellular calcium levels, and the phorbol myristate acetate (PMA)-induced edema model were used to investigate how LA inhibits the production of TSLP in HMC-1 cells. LA reduced the production and mRNA expression of TSLP in HMC-1 cells. LA also inhibited the activation of nuclear factor-κB and degradation of IκBα. PMA plus A23187 stimulation up-regulated caspase-1 activity in HMC-1 cells; however, this up-regulated caspase-1 activity was down-regulated by LA. Finally, LA decreased intracellular calcium levels in HMC-1 cells as well as PMA-induced ear swelling responses in mice. Taken together, these results suggest that LA would be beneficial to treatment of atopic and inflammatory diseases by reducing TSLP.

Surface Design of Separators for Oil/Water Separation with High Separation Capacity and Mechanical Stability.

A convection heat treatment that can replace existing chemical oxidation methods was developed for the preparation of hierarchically oxidized Cu meshes with various surface morphologies, representing a very simple and green route that does not involve toxic chemicals. Three types of Cu meshes [bumpy-like (BL) and short and long needle-like (NL) structures] exhibited similar separation efficiencies of 95-99% over 20 separation cycles, as indicated by their similar water contact angles (WCAs; 147-150°). However, these Cu meshes exhibited different flux behaviors. Excessively rough and excessively smooth surfaces of the Cu mesh resulted in increased resistance to flow and to a decrease of the penetration of oil. A surface with intermediate smoothness, such as the BL-Cu mesh, was necessary for high flux over a broad range of oil viscosities. Furthermore, a less rough surface was more suitable for the separation of highly viscous oil. Computational fluid dynamics (CFD) simulations were carried out to support our experimental results. The BL-Cu meshes also showed outstanding mechanical stability because of their low resistance to the flow of fluids.

Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), an anticancer agent, exerts an anti-inflammatory effect in activated human mast cells.

OBJECTIVE: Inflammation has been closely associated with the development and progression of cancer. Previously, we reported that mast cells play a critical role in tumor growth. The purpose of this study is to investigate the anti-inflammatory effect of an anticancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), on an activated human mast cell line, in this case HMC-1 cells. METHODS: We evaluated the effect and specific molecular mechanism of Dp44mT on phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI) using HMC-1 cells. RESULTS: Here, we demonstrated that Dp44mT significantly decreased the protein levels of hypoxia-inducible factor-1α and vascular endothelial growth factor without exposing activated HMC-1 cells to any cytotoxicity. In activated mast cells, Dp44mT mitigated the strong production and mRNA expression of inflammatory cytokines, in this case, interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and thymic stromal lymphopoietin, through a blockade of caspase-1 and nuclear factor-κB activities. Furthermore, phosphorylations of the mitogen-activated protein kinase family included in inflammatory signaling cascades were significantly inhibited by a Dp44mT treatment. CONCLUSIONS: Overall, our results indicate that the anticancer agent Dp44mT has an anti-inflammatory effect and may be of therapeutic importance for the treatment of mast cell-mediated inflammatory diseases.

ß-eudesmol suppresses allergic reactions via inhibiting mast cell degranulation.

The regulatory effect of ß-eudesmol, which is an active constituent of Pyeongwee-San (KMP6), is evaluated for allergic reactions induced by mast cell degranulation. Phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cell line, HMC-1 cells, and compound 48/80-stimulated rat peritoneal mast cells (RPMCs) are used as the in vitro models; mice models of systemic anaphylaxis, ear swelling, and IgE-dependent passive cutaneous anaphylaxis (PCA) are used as the in vivo allergic models. The results demonstrate that ß-eudesmol suppressed the histamine and tryptase releases from the PMA plus calcium ionophore A23187-stimulated HMC-1 cells. ß-eudesmol inhibits the expression and activity of histidine decarboxylase in the activated HMC-1 cells. In addition, ß-eudesmol inhibits the levels of histamine and tryptase released from the compound 48/80-stimulated RPMCs. Furthermore, ß-eudesmol decreases the intracellular calcium level in the activated RPMCs. ß-eudesmol also decreases the compound 48/80-induced mortality and ear swelling response. ß-eudesmol suppresses the serum levels of histamine, IgE, interleukin (IL)-1ß, IL-4, IL-5, IL-6, IL-13, and vascular endothelial growth factor (VEGF) under PCA mice as well as PCA reactions. Therefore, the results from this study indicate the potential of ß-eudesmol as an anti-allergic drug with respect to its pharmacological properties against mast cell-mediated allergic reactions.

Protective effect of porcine placenta in a menopausal ovariectomized mouse.

Menopause is a significant physiological phase that occurs as women's ovaries stop producing ovum and the production of estrogen declines. Human placenta and some amino acids are known to improve menopausal symptoms. In this study, we investigated that porcine placenta extract (PPE) and arginine (Arg), a main amino acid of PPE, would have estrogenic activities in ovariectomized (OVX) mice as a menopause mouse model, human breast cancer cell line (MCF-7) cells, and human osteoblast cell line (MG-63) cells. PPE or Arg significantly inhibited the body weight and increased the vagina weight compared to the OVX mice. PPE or Arg ameliorated the vaginal atrophy in the OVX mice. The levels of 17ß-estradiol and the activities of alkaline phosphatase (ALP) were significantly increased by PPE or Arg in the serum of OVX mice. Trabecular bone parameters such as bone mineral density and porosity were also improved by PPE or Arg in the OVX mice. In the MCF-7 and MG-63 cells, PPE or Arg significantly increased the cell proliferation, estrogen receptor ß mRNA expression, and estrogen-response elements luciferase activity. Finally, PPE or Arg increased the activations of ALP and extracellular signal-regulated kinase 1/2 in the MG-63 cells. These results indicate that PPE or Arg would have estrogenic and osteoblastic activity. Therefore, PPE or Arg may be useful as new pharmacological tools for treating menopausal symptoms including osteoporosis. Free Korean abstract: A Korean translation of this abstract is freely available at http://www.reproduction-online.org/content/150/3/173/suppl/DC1.

The potential anti-proliferative effect of ß-sitosterol on human mast cell line-1 cells.

Thymic stromal lymphopoietin (TSLP) was reported to induce mast cell proliferation and aggravate allergic reactions through activation of mouse double minute 2 (MDM2). We aimed to ascertain that ß-sitosterol (SI), which is one of the several phytosterols found mostly in foods, would regulate TSLP-induced mast cell proliferation. The results showed that SI significantly decreased the proliferation of human mast cell line (HMC-1) cells promoted by TSLP. SI significantly decreased the mRNA expression of Ki-67 in the TSLP-treated HMC-1 cells. SI significantly suppressed the production and mRNA expression of interleukin-13 in the TSLP-treated HMC-1 cells. Furthermore, SI downregulated the expression of MDM2 and phosphorylation of STAT6, whereas it upregulated the expression of p53, activation of caspase-3, and cleavage of poly ADP-ribose polymerase in the TSLP-treated HMC-1 cells. Results of this study suggest that SI may be a potential therapeutic agent for mast cell-mediated allergic diseases.

Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP.

Atopic dermatitis (AD) is a common skin disease that greatly worsens quality of life. Thymic stromal lymphopoietin (TSLP) plays a decisive role in the development of AD. The purpose of this study is to examine whether tryptanthrin (TR) would suppress AD through the regulation of TSLP. We analyzed the effect of TR on the level of TSLP from phorbol myristate acetate/calcium ionophore A23187-activated human mast cell line, HMC-1 cells, in 2,4-dinitrofluorobenzene-induced AD-like skin lesions of NC/Nga mice, and in anti-CD3/anti-CD28-stimulated splenocytes. TR significantly suppressed the level of intracellular calcium and the production and mRNA expression of TSLP through the blockade of receptor-interacting protein 2/caspase-1/nuclear factor-κB pathway in the activated HMC-1 cells. TR also significantly suppressed the levels of histidine decarboxylase and IL-1ß. Furthermore, TR ameliorated clinical symptoms in the AD model. TR significantly reduced the levels of TSLP, IL-4, IFN-γ, IL-6, TNF-α, thymus and activation-regulated chemokine, and caspase-1 in AD skin lesions. Also, TR significantly reduced the serum levels of histamine and IL-4 in the AD model. Finally, TR significantly inhibited the production of IL-4, IFN-γ, and TNF-α from the stimulated splenocytes. Taken together, TR exhibits the potential to be a therapeutic agent for AD through down-regulation of TSLP.

Hyperoside regulates the level of thymic stromal lymphopoietin through intracellular calcium signalling.

Hyperoside (HYP) is the principle active component of Crataegus pinnatifida. Thymic stromal lymphopoietin (TSLP) plays a vital role in the pathogenesis of allergic reactions. Here, we investigated how HYP regulates the levels of TSLP in a human mast cell line, HMC-1 cells. We analyzed the levels of TSLP by treatment with HYP in phorbol myristate acetate plus calcium ionophore A23187-stimulated HMC-1 cells with ELISA and a polymerase chain reaction analysis. We also analyzed the pathway that HYP regulates TSLP by measuring the level of fluorescent intracellular calcium and using a Western blot analysis. HYP decreased the level of intracellular calcium in stimulated HMC-1 cells. It also significantly decreased the production and mRNA expression of TSLP in stimulated HMC-1 cells. It significantly decreased the levels of receptor-interacting protein 2 and active caspase-1 in stimulated HMC-1 cells. HYP significantly decreased the translocation of NF-κB into the nucleus and degradation of IκBα in the cytoplasm in stimulated HMC-1 cells. Furthermore, it significantly decreased the production and mRNA expression of interleukin-1ß and interleukin-6 in stimulated HMC-1 cells. Taken together, our findings establish HYP as a potential agent for the treatment of allergic reactions.