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Anti-Allergic and Anti-Inflammatory Effects of Kuwanon G and Morusin on MC/9 Mast Cells and HaCaT Keratinocytes.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. The use of immunomodulatory corticosteroids in AD treatment causes adverse side effects. Therefore, novel natural anti-inflammatory therapeutics are needed. The aim of the present study was to investigate the anti-allergic and anti-inflammatory activities of kuwanon G and morusin. To investigate the effect of kuwanon G and morusin on skin inflammation, enzyme-linked immunosorbent assays (ELISA) to quantitate secreted (RANTES/CCL5), thymus- and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22) were performed, followed by Western blotting to measure the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and nuclear transcription factor-κB (NF-κB) p65 in tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-stimulated HaCaT keratinocytes. In order to evaluate the anti-allergic effects, ELISA to quantify histamine and leukotriene C₄ (LTC₄) production and Western blotting to measure 5-lipoxygenase (5-LO) activation were performed using PMA and A23187-stimulated MC/9 mast cells. Kuwanon G reduced the release of RANTES/CCL5, TARC/CCL17, and MDC/CCL22 via down-regulation of STAT1 and NF-κB p65 signaling in TNF-α and IFN-γ-stimulated HaCaT keratinocytes. Kuwanon G also inhibited histamine production and 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Morusin inhibited RANTES/CCL5 and TARC/CCL17 secretion via the suppression of STAT1 and NF-κB p65 phosphorylation in TNF-α and IFN-γ-stimulated HaCaT keratinocytes, and the release of histamine and LTC₄ by suppressing 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Kuwanon G and morusin are potential anti-inflammatory mediators for the treatment of allergic and inflammatory skin diseases such as AD.

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Rhododendron album Blume extract inhibits TNF-α/IFN-γ-induced chemokine production via blockade of NF-κB and JAK/STAT activation in human epidermal keratinocytes.

Rhododendron album Blume (RA) has traditionally been used as an herbal medicine and is considered to have anti‑inflammatory properties. It is a well‑known medicine for treatment of allergic or atopic diseases. In the present study, the biological effects of an RA methanol extract (RAME) on inflammation were investigated in tumor necrosis factor‑α (TNF‑α)/interferon‑γ (IFN‑γ)‑stimulated human keratinocytes. The present study aimed to investigate the potential mechanisms by which RAME inhibited TNF‑α/IFN‑γ‑induced expression of chemokines [thymus‑ and activation-regulated chemokine (TARC) and macrophage‑derived chemokine (MDC)] and cytokines [interleukin (IL)‑6 and IL‑8] through the nuclear factor‑κB (NF‑κB) pathway in human keratinocytes. The effects of RAME treatment on cell viability were investigated in TNF‑α/IFN‑γ‑stimulated HaCaT cells. The expression of TARC, MDC, IL‑6 and IL‑8 was assessed using reverse transcription‑quantitative polymerase chain reaction analysis or ELISA, and its effect on the inhibitory mitogen-activated protein kinase pathway was also studied using western blot analysis. TNF‑α/IFN‑γ induced the expression of IL‑6, IL‑8, TARC and MDC in a dose‑dependent manner through NF‑κB and Janus kinase/signal transducers and activators of transcription (JAK/STAT) activation. Notably, treatment with RAME significantly suppressed TNF-α/IFN-γ-induced expression of IL‑6, IL‑8, TARC, and MDC. In addition, RAME treatment inhibited the activation of NF‑κB and the JAK/STAT pathway in TNF‑α/IFN‑γ‑induced HaCaT cells. These results suggest that RAME decreases the production of chemokines and pro‑inflammatory cytokines by suppressing the NF‑κB and the JAK/STAT pathways. Consequently, RAME may potentially be used for treatment of atopic dermatitis.

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Effect of peiminine on DNCB-induced atopic dermatitis by inhibiting inflammatory cytokine expression in vivo and in vitro.

Peiminine (PMN) is the main component derived from Fritillaria ussuriensis and is used in traditional medicine in East Asia. The aim of this study was to evaluate the effects of PMN on atopic dermatitis (AD) induced by a dinitrochlorobenzene (DNCB) in Balb/c mice. Inflammatory cytokine expression of PMN was investigated in vitro. Eosinophil infiltration and the thickness of DNCB-induced AD mouse skin were measured. The levels of IgE, IL-4, IL-6, IL-13, and TNF-α in the serum were measured by ELISA. The effects of PMN on the transcription level of MAPK and nuclear factor (NF)-κB were evaluated in mouse skin. In addition, the inhibitory effect of TNF-α, IL-1β, COX-2 and PGE2 were measured in RAW264.7 cells; TARC was investigated in HaCaT cells; and β-hexosaminidase was examined in RBL-2H3 cells. PMN decreased the number of eosinophils in the dermis as well as mast cells and decreased the thickness of the epidermis and dermis. The PMN High group had a significantly reduced serum level of IgE, IL-4, IL-13 and TNF-α. Moreover, P-ERK and P-P38 were inhibited in the PMN High group compared with the DNCB-treated group. PMN additionally attenuated the expression of inflammatory cytokines in cells, including RAW264.7, HaCaT and RBL-2H3 cells. Our results suggest that PMN could be a potential therapeutic candidate for the treatment of AD.

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Effect of haemolysis on the determination of CCL17/thymus and activation-regulated chemokine (TARC) and CCL22/macrophage-derived chemokine (MDC).


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Serum levels of squamous cell carcinoma antigens 1 and 2 reflect disease severity and clinical type of atopic dermatitis in adult patients.

Recent studies have indicated that serum levels of squamous cell carcinoma antigen (SCCA) 1 and 2 induced by type 2 cytokines such as IL-4 and IL-13, are increased in patients with atopic dermatitis (AD). However, no clinical studies have analyzed serum levels of SCCA2 in larger series of AD patients or their association with various clinical characteristics. This study was performed to clarify whether serum levels of SCCA2 are associated with disease severity and clinical phenotypes of adult AD patients.

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Intracellular Storage of Duffy Antigen-Binding Chemokines by Duffy-Positive Red Blood Cells.

Duffy antigen/chemokine receptor (DARC) is a non-signaling receptor for multiple chemokines. The role of DARC on red blood cells (RBCs) has remained elusive. The purpose of this study was to analyze selective storage of DARC-binding chemokines in RBCs.

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Inhibitory effect of Patrinia scabiosifolia Link on the development of atopic dermatitis-like lesions in human keratinocytes and NC/Nga mice.

Atopic dermatitis (AD) is a chronic pruritic and inflammatory disease occurring in skin. Patrinia scabiosifolia Link (PS), a member of the Patrinia genus (Caprifoliaceae family), has traditionally been used in folk medicines to treat various inflammatory diseases such as acute appendicitis, ulcerative colitis, and pelvic inflammation in Korea and other parts of East Asia.

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[Circulating levels of Th1- and Th2-chemokines increase in patients with early syphilis].

Objective To study the changes of plasma T helper type I (Th1)-and Th2-chemokine levels and analyze their roles in immune response and pathogenesis of early syphilis. Methods Heparin-anticoagulated peripheral blood was collected from 56 patients with early syphilis (primary syphilis, PS, n=22; secondary syphilis, SS, n=34) and healthy controls (HC, n=20). The levels of plasma Th1 chemokines including monokine induced by interferon-γ (MIG), interferon-γ inducible protein-10 (IP-10), interferon-inducible T-cell α chemoattractant (I-TAC) and Th2 chemokines including thymus-and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) were examined using ELISA. Meanwhile, the levels of plasma cytokines (IFN-γ, IL-4 and TNF-α) and C-reactive protein (CRP) were detected. Results The levels of plasma MIG, IP-10 and TARC, MDC in the patients with PS and SS were significantly higher than those in the healthy controls. Moreover, the level of I-TAC in the patients with SS was significantly higher than that in the healthy controls. In particular, the levels of plasma Th1 chemokines (MIG, IP-10 and I-TAC) in the patients with SS significantly increased compared with those with PS. However, no significant difference was observed in the levels of plasma Th2 chemokines (TARC and MDC) between the patients with PS and SS. The correlation analysis showed that there was an obvious positive correlation between IP-10 and MIG, I-TAC, IFN-γ, TNF-α levels in the patients with early syphilis. Furthermore, the levels of MIG and IP-10 were positively associated with plasma CRP in the patients with early syphilis. Conclusion Both Th1 chemokines and Th2 chemokines are involved in immune response of early syphilis.

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Increased sputum levels of thymus and activation-regulated chemokine in children with asthma not eosinophilic bronchitis.

Thymus and activation-regulated chemokine (TARC), a member of the CC chemokine family, plays a crucial role in Th2-specific inflammation. We aimed to determine the concentration of sputum TARC in children with asthma and eosinophilic bronchitis (EB) and its relation with eosinophilic inflammation, pulmonary function, and bronchial hyper-responsiveness.

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Clinical Usefulness of Simultaneous Measurement of the Tear Levels of CCL17, CCL24, and IL-16 for the Biomarkers of Allergic Conjunctival Disorders.

This study investigated the clinical usefulness of a multiple tear cytokine/chemokine test by simultaneously determining tear levels of CC chemokine ligand 17 (CCL17)/thymus and activation-regulated chemokine (TARC), CCL24/eotaxin-2, and interleukin-16 (IL-16) for assessing acute and chronic allergic inflammation in allergic conjunctival disorders (ACDs).

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