• CELLMED
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• v.6 no.3
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• pp.16.1-16.5
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• 2016

Thymic stromal lymphopoietin (TSLP) is a novel interleukin (IL)-7-like cytokine and was originally discovered in the supernatant of a murine thymic stromal cell line. TSLP signal initiates via complex of the TSLP receptor and the IL-7 receptor α chain. TSLP expression is closely connected with many diseases such as atopic dermatitis, allergic rhinitis, asthma, inflammatory arthritis, eosinophilic esophagitis, rheumatoid arthritis, inflammatory bowel diseases, and cancer. In this review, I discussed biological roles of TSLP on mast cell-mediated allergic responses. In addition, this review summarizes the effective drugs in allergic-inflammatory reactions induced by TSLP on mast cells.

• Childhood Kidney Diseases
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• v.22 no.1
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• pp.17-21
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• 2018

Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine that is an important trigger and initiator of many allergic diseases. TSLP promotes a T-helper type 2 (Th2) cytokine response that can be pathological. A relationship is formed both at the induction phase of the Th2 response through polarization of dendritic cells to drive Th2 cell differentiation and at the effector phase of the response, by promoting the expansion of activated T cells and their secretion of Th2 cytokines and TSLP. In transgenic mice with TSLP overexpression, it has been reported that TSLP leads to the development of mixed cryoglobulinemic membranoproliferative glomerulonephritis. In addition, TSLP can play an important role in the pathogenesis of IgA nephropathy and systemic lupus erythematosus-related nephritis. From our knowledge of the role of TSLP in the kidney, further studies including the discovery of new therapies need to be considered based on the relationship between TSLP and glomerulonephritis.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.176-182
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• 2021

Background: Atopic dermatitis (AD) is associated with chronic skin inflammatory reactions. p-coumaric acid (pCA) is an active ingredient of Panax ginseng Meyer (Araliaceae). Methods: Here, we estimated an anti-AD effect of pCA on activated mast cells, activated splenocytes, and a mouse model of AD. Cytokines levels were measured by ELISA and protein activation was analyzed by Western blotting. 2,4-dinitrofluorobenzene (DNFB) was used to induce AD-like skin lesions. Results: The treatment with pCA suppressed the productions and mRNA expressions of thymic stromal lymphopoietin (TSLP), TNF-α, IL-6, and IL-1β in HMC-1 cells. pCA downregulated the expressions of RIP2 and caspase-1, phosphorylated-(p)p38/pJNK/pERK, and pIKKβ/pIkBα/NF-κB in HMC-1 cells. pCA also decreased the productions of TSLP, TNF-α, IL-6, IL-4, and IFN-γ in the supernatant of stimulated splenic cells. Comparing to DNFB-sensitized control group, pCA-treated group alleviated pathological changes of AD-like lesions. pCA decreased the proteins and mRNA expressions levels of TSLP, IL-6, and IL-4 in the skin lesions. Caspase-1 activation was also downregulated by pCA treatment in the AD-like lesions. The serum levels of histamine, IgE, TSLP, TNF-α, IL-6, and IL-4 were suppressed following treatment with pCA. Conclusion: This study suggests that pCA has the potential to improve AD by suppressing TSLP as well as inflammatory cytokines via blocking of caspase-1/NF-κB signal cascade.

• Journal of Life Science
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• v.22 no.1
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• pp.25-30
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• 2012

Thymic stromal lymphopoietin(TSLP) is a novel IL-7-like hematopoietic cytokine. Human TSLP is produced by epithelial cells, stromal cells, and mast cells. The TSLP gene is highly expressed in synovial fluid specimens derived from rheumatoid arthritis (RA) patients. We previously identified four single nucleotide polymorphisms (SNPs) and one variation site in human TSLP gene. In this study, we analyzed the genotypic and allelic frequencies of the TSLP SNPs between RA patients and healthy controls. We also investigated the relationships between SNP genotypes and the RF levels and anti-synthetic cyclic citrullinated peptide (CCP) levels in RA patients. We then calculated the haplotype frequencies defined by these SNPs for both groups. The genotype and allele frequencies of the TSLP SNPs did not differ significantly between the RA patients and the healthy controls. We also found that TSLP SNPs in the RA patients had no significant association with the levels of RF or anti-CCP. Our results suggest that TSLP SNPs are not associated with susceptibility to RA.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.481-486
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• 2018

Cosmetics are primarily applied to the skin; therefore, the association of cosmetic dyes with skin diseases or inflammation is a topic of great interest. Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine that activates dendritic cells to promote Th2 inflammatory immune responses. TSLP is highly expressed in keratinocytes under inflammatory conditions, which suggests that it may play a critical role in the development of skin diseases, such as atopic dermatitis. Therefore, we investigated whether cosmetic dyes influenced the production of TSLP by keratinocytes. Phloxine O, also known as D&C Red No.27, is one of the most common red synthetic pigments and is widely used in colored cosmetics. Our results showed that Phloxine O downregulated phorbol 12-myristate 13-acetate-induced production of TSLP in a murine keratinocyte cell line (PAM212). Phloxine O also suppressed TSLP expression in KCMH-1 cells, which are mouse keratinocytes that constitutively produce high levels of TSLP. To investigate the in vivo effects of Phloxine O, we induced TSLP expression in mouse ear skin by topically applying MC903, a vitamin D3 analogue that is a well-known inducer of atopic dermatitis-like symptoms. Topical application of Phloxine O prevented MC903-induced TSLP production in mouse ear skin, attenuated the acute dermatitis-like symptoms and decreased serum IgE and histamine levels in mice. Suppression of TSLP expression by Phloxine O correlated with reduced expression of OX40 ligand and Th2 cytokines in mouse ear skin. Our results showed that Phloxine O may be beneficial to prevent dermatitis by suppressing the expression of TSLP and Th2 cytokines in skin.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.610-616
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• 2021

Background: Thymic stromal lymphopoietin (TSLP) acts as a master switch for inflammatory responses. Ginsenoside Rg3 (Rg3) which is an active ingredient of Panax ginseng Meyer (Araliaceae) is known to possess various therapeutic effects. However, a modulatory effect of Rg3 on TSLP expression in the inflammatory responses remains poorly understood. Methods: We investigated antiinflammatory effects of Rg3 on an in vitro model using HMC-1 cells stimulated by PMA plus calcium ionophore (PMACI), as well as an in vivo model using PMA-induced mouse ear edema. TSLP and vascular endothelial growth factor (VEGF) levels were detected using enzyme-linked immunosorbent assay or real-time PCR analysis. Murine double minute 2 (MDM2) and hypoxia-inducible factor 1α (HIF1α) expression levels were detected using Western blot analysis. Results: Rg3 treatment restrained the production and mRNA expression levels of TSLP and VEGF in activated HMC-1 cells. Rg3 down-regulated the MDM2 expression level increased by PMACI stimulation. The HIF1α expression level was also reduced by Rg3 in activated HMC-1 cells. In addition, Rg3-administered mice showed the decreased redness and ear thickness in PMA-irritated ear edema. Rg3 inhibited the TSLP and VEGF levels in the serum and ear tissue homogenate. Moreover, the MDM2 and HIF1α expression levels in the ear tissue homogenate were suppressed by Rg3. Conclusion: Taken together, the current study identifies new mechanistic evidence about MDM2/HIF1α pathway in the antiinflammatory effect of Rg3, providing a new effective therapeutic strategy for the treatment of skin inflammatory diseases.

• Toxicological Research
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• v.28 no.3
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• pp.159-164
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• 2012

Allergic skin inflammation such as atopic dermatitis (AD) is characterized by edema and infiltration with various inflammatory cells such as mast cells, basophils, eosinophils and T cells. Thymic stromal lymphopoietin (TSLP) is produced mainly by epidermal keratinocytes, as well as dermal fibroblasts and mast cells in the skin lesions of AD. Omega-3 polyunsaturated fatty acids in fish oil can reduce inflammation in allergic patients. Fermentation has a tremendous capacity to transform chemical structures. The antiinflammatory effects of fish oil have been described in many diseases, but the beneficial effects by which fermented olive flounder oil (FOF) modulates the allergic response is poorly understood. In this study, we produced FOF and tested its ability to suppress the various allergic inflammatory responses. The ability of FOF to modulate the immune system was investigated using a mouse model of AD. The FOF-treated group showed significantly decreased immunoglobulin E (IgE) and histamine in serum. Also, the increased TSLP expression was significantly inhibited in the FOF group; the FOF-treated group was not appreciably different from the hydrocort cream treatment group. In addition, FOF treatment resulted in a smaller spleen size with reduced the thickness and length compared to the induction group. Splenocytes from mice treated with FOF produced significantly less IFN-${\gamma}$, IL-4, T-box transcription factor (T-bet) and GATA binding protein 3 (GATA3) expression compared with the induction group. These results suggest that FOF may be effective in treating the allergic symptoms of AD. 5.

• Parasites, Hosts and Diseases
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• v.49 no.3
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• pp.235-243
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• 2011

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.

• The Journal of Pediatrics of Korean Medicine
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• v.35 no.3
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• pp.128-137
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• 2021

Objective The purpose of this study was to confirm the effectiveness of coptidis rhizoma extract-ceramide complex on skin barrier, transepidermal water loss (TEWL) and pH reduction, and inflammation of the skin. Methods Coptidis rhizoma extract-ceramide complex was applied in 6-week-old Balb/C mice after dermatitis was induced. To confirm the skin condition changes, TEWL and pH were observed, and filaggrin in the stratum corneum of the skin was observed. Kallikrein-related peptidase (KLK) 7, Protease activated receptor (PAR)-2, Thymic stromal lymphopoietin (TSLP), and IL-4 were observed in the stratum corneum to confirm the changes in the inflammatory response. Results Filaggrin positive reaction was increased in the experiment group compared to the control group. TEWL and pH were lower in the experiment group compared to the control group. KLK7, PAR2, TSLP, and IL-4 positive responses were decreased in the experiment group compared to the control group. Conclusions It was confirmed that the coptidis rhizoma extract-ceramide complex can relieve the inflammatory response of atopic dermatitis by restoring the skin lipid barrier damage.

• Journal of Life Science
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• v.27 no.5
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• pp.600-610
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• 2017

It was common that the classification of itching was classified into four categories according to the neurophysiological mechanisms of pruritoceptive itching, neuropathic itching, neurogenic itching and psychogenic itching. Recently it was classified by clinical criteria. The neurotransmission pathway of itch is divided into histamine-dependent pathway and histamine-independent pathway. Different receptors and neuropeptides act on each itch mediator. Itch mediators such as histamine, BAM8-22, and chloroquine are transmitted through the histamine-dependent pathway. Cowhage spicule, protease, and TSLP (Thymic stromal lymphopoietin) have been reported to be related to the histamine-independent pathway. These itch mediators, receptors, and neuropeptides are the targets of treatment for itching. Although itching and pain are typical noxious stimuli, and in the past, it was argued that two senses were transmitted through one noxious stimulus receptor. It has recently been shown that itching and pain have an independent neurotransmitter system and both neuronal systems inhibit each other. In addition, the mutual antagonism between itching and pain is explained by various mechanisms. Recently, many new mediators and receptors are being studied. The studies on histamine 4 receptor (H4 receptor) have been actively conducted. And the H4 receptors are expressed in immune cells such as T cells. The therapeutic agent for blocking the H4 receptor can inhibit the inflammatory reaction itself, which is important for the itching and chronicization. Understanding the underlying mechanisms of itching and studying new itch mediators will lead to the development of effective therapies, and this is what I think the itching study will go on.