• 약학회지
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• 제50권2호
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• pp.105-110
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• 2006

The effects of tributyltin acetate (TBTA), one of the endocrine-disrupting organotin compounds, on dopamine biosynthesis in PC12 cells were investigated. Treatment of PC12 cells with TBTA at $0.05\sim0.25{\mu}M$ significantly decreased the intracellular dopamine content in a concentration-dependent manner ($IC_{50}$ value, $0.17{\mu}M$). Under these conditions, tyrosine hydroxylase (TH) activity and TH mRNA level were also decreased by $0.1{\mu}M$ TBTA at 24 h, and recovered there-after. In addition, treatment with L-DOPA at 20 and $50 {\mu}M$ increased the intracellular dopamine content in PC12 cells and the increase in dopamine content by L-DOPA was significantly abolished by TBTA at $0.1\sim0.2{\mu}M$. These results indicate that TBTA at $0.1\sim0.2{\mu}M$ causes the decrease in the basal dopamine content and abolishes the increase in dopamine content in L-DOPA-treated cells in part by the inhibition of TH gene expression and activity.

• 한국식품영양학회지
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• 제36권6호
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• pp.452-461
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• 2023

Hypertension caused by high-fat and high-salt diets is is a well-known significant risk factor for cardiovascular and cerebrovascular diseases. In this study, to confirm the relationship between hypertension and immune cells, angiotensin (Ang) II was administered to Dahl salt-sensitive (SS) rats and Dahl salt-resistant (SR) rats. Then the expression of immune cells and the proinflammatory cytokines were compared between the SS and SR rats. It was observed that after administration of Ang II (50ng/kg/min) for three weeks, blood pressure was increased in the SS rats, but there was no significant change in the SR rats. In addition, the expression of T helper (Th) cells and Th 17 cells in the spleen and the expression of Th cell Rorγt and regulatory T regulatory (Treg) cells in the peripheral blood mononuclear cells did not show a significant difference between the two experimental groups even after the administration of Ang II.IL-1β expression was significantly increased in the kidney tissue of the SS rats, while there was no significant difference in the IL-6 expression in all the experimental groups. The results of this study suggest that Ang II induces hypertension by stimulating IL-1β secretion from renal macrophage in SS rats.

• IMMUNE NETWORK
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• 제22권6호
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• pp.46.1-46.25
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• 2022

T-helper-17 (Th17) cells and related IL-17-producing (type17) lymphocytes are abundant at the epithelial barrier. In response to bacterial and fungal infection, the signature cytokines IL-17A/F and IL-22 mediate the antimicrobial immune response and contribute to wound healing of injured tissues. Despite their protective function, type17 lymphocytes are also responsible for various chronic inflammatory disorders, including inflammatory bowel disease (IBD) and colitis associated cancer (CAC). A deeper understanding of type17 regulatory mechanisms could ultimately lead to the discovery of therapeutic strategies for the treatment of chronic inflammatory disorders and the prevention of cancer. In this review, we discuss the current understanding of the development and function of type17 immune cells at the intestinal barrier, focusing on the impact of microbiota-immune interactions on intestinal barrier homeostasis and disease etiology.

• The Korean Journal of Physiology and Pharmacology
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• 제23권4호
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• pp.251-261
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• 2019

Allergic asthma, is a common chronic inflammatory disease of the airway presenting with airway hyperresponsiveness and airway remodelling. T helper cells-derived cytokines are critically associated with asthma pathogenesis. Janus kinase-signal transduction and activation of transcription (JAK/STAT) signaling is found to be involved in asthma. Magnolol is a plant-derived bioactive compound with several pharmacological effects. The study aimed to assess the effects of magnolol in ovalbumin (OVA)-induced asthmatic model. BALB/c mice were sensitized and challenged with OVA. Magnolol (12.5, 25, or 50 mg/kg body weight) was administered to separate groups of animals. Dexamethasone was used as the positive control. Cellular infiltration into the bronchoalveolar lavage fluid (BALF) were reduced on magnolol treatment. The levels of Th2 and Th17 cytokines were reduced with noticeably raised levels of interferon gamma. Lung function was improved effectively along with restoration of bronchial tissue architecture. OVA-specific immunoglobulin E levels in serum and BALF were decreased by magnolol. Magnolol reduced Th17 cell population and effectively modulated the JAK-STAT and Notch 1 signaling. The results suggest the promising use of magnolol in therapy for allergic asthma.

• 대한의생명과학회지
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• 제21권2호
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• pp.122-125
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• 2015

House dust mite (HDM) as a major allergen and damage-associated molecular pattern (DAMP) such as S100A8 and S100A9 trigger the pathogenesis and severity of allergic disease such as asthma. Regulation of neutrophil apoptosis is an important immune response and its dysregulation is involved in pathogenesis of allergic diseases. In this study, we examined the effects of HDM, S100A8 and S100A9 on spontaneous apoptosis of normal neutrophils. We considered the importance of the difference between in vitro and in vivo results and developed a new in vitro system consisting of a combination of immune cells and T helper (Th) cytokines. Extract of Dermatophagoides pteronyssinus (DP), S100A8, and S100A9 inhibited neutrophil apoptosis in culture of neutrophils alone without other leukocytes. DP and S100A8 more strongly suppressed neutrophil apoptosis in combinations of neutrophils, eosinophils, lymphocytes or monocytes than in a culture of neutrophils alone. Anti-apoptotic effect of S100A9 in the mixture of immune cells was similar to that in neutrophils. DP, S100A8, and S100A9 blocked neutrophil apoptosis, regardless of pretreatment with a T helper (Th) 1 cytokine (IFN-$\gamma$), Th2 cytokines (IL-4 and IL-10), a Th9 cytokine (IL-9), a Th17 cytokine (IL-17), a Treg-producing cytokine (TGF-$\beta$). These findings may enable elucidation of allergy pathogenesis due to HDM and DAMP.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.611-618
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• 2023

Rhizome of Alisma orientale has been used as a traditional medicine for treating kidney diseases in East Asian countries. Its inhibitory effects on hypersensitivity responses have been reported for methanol extracts, with alisol B 23-acetate (AB23Ac) being the most active constituent among six terpenes in inhibiting the direct passive Arthus reaction. However, whether AB23Ac has efficacy against allergic asthma has not been tested to date. The in vivo efficacy of AB23Ac in an ovalbumin (OVA)-induced allergic asthma mouse model was evaluated by administrating AB23Ac before OVA sensitization or OVA challenge in BALB/c mice. AB23Ac suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of AB23Ac both before OVA sensitization and OVA challenge greatly lowered pulmonary resistance and the increase in immune cell counts and inflammatory responses around the peribronchial and perivascular regions. In addition, the inflammatory cytokine levels of Th1/Th2/Th17 cells in the bronchoalveolar lavage fluid decreased in the AB23Ac-treated groups. AB23Ac reduced the number of PAS-stained cells in the lungs. Furthermore, a computer modeling study indicated that AB23Ac can bind tightly to spleen tyrosine kinase (Syk). These results suggest that AB23Ac may ameliorate allergic asthma by suppressing immune responses in dendritic cells during sensitization and in mast cells during challenge periods.

• 한양메디칼리뷰
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• 제33권1호
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• pp.10-16
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• 2013

Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORγt. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORγt, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.

• Journal of Ginseng Research
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• 제44권6호
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• pp.815-822
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• 2020

Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. Methods: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. Results: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3⁺ regulatory T cells (Tregs) increased but IL-17-producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORgt expression and stimulating Foxp3 expression. Conclusion: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.

• Journal of Applied Biological Chemistry
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• 제63권1호
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• pp.95-101
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• 2020

건선(psoriasis)은 인체 피부조직 중 표피의 과증식 및 다양한 크기의 홍반, 인설 등이 동반되는 난치성 자가면역 피부질환이다. 건선 피부염 발병 기작은 명확히 규명되지 않았으나 각질 형성세포의 과분화 과정에 관여하는 염증성 cytokine과 Th17 세포를 포함한 면역세포를 염증부위로 유인하는 chemokine (C-C motif) ligand 20 (CCL20)이 발병과정에 관여하는 것으로 알려진다. 따라서 건선치료에 효과적인 천연 소재를 발굴하기 위해 예로부터 항염증 활성이 알려진 익지인(Alpiniaoxyphylla Miquel)의 유효성분인 yakuchinone-A의 건선 피부염 개선효과를 연구하였다. 먼저 CCK-8 assay 통해 human keratinocyte (HaCaT) 세포에 tumor necrosis factor-alpha (TNF-α)와 yakuchinone-A를 동시 처리하여 세포독성을 관찰한 결과, yakuchinone-A는 10 ㎍/mL까지 세포독성이 관찰되지 않았다. TNF-α를 HaCaT 세포에 처리하여 염증을 유발한 후 yakuchinone-A를 농도별로 처리한 결과 IL-6, IL-8, TNF-α 등 건선 피부염 유발 cytokine의 mRNA 발현이 각각 61.4±7.5, 23.6±1.5, 46.0±4.8% 수준으로 감소하였고, Th17 세포를 유인하는 chemokine인 CCL20 또한 yakuchinone-A에 의해 유의적으로 억제되었다. 또한 CCL20 발현에 관여하는 NF-κB/IκB pathway에서 IκB 인산화 및 STAT3 인산화가 yakuchinone-A에 의해 79.1±5.0, 80.8±2.3% 수준만큼 농도 의존적으로 억제되었다. 마지막으로 Th17 세포에 의해 분비되는 IL-17A에 의해 활성화된 HaCaT 세포에 yakuchinone-A를 처리한 결과, CCL20 mRNA발현이 농도의존적으로 감소하였다. 이러한 결과들을 토대로 yakuchinone-A는 건선 피부염 개선 활성을 가지며, 향후 새로운 건선 피부염 개선 소재로 개발될 수 있을 것으로 기대된다.

• The Korean Journal of Physiology and Pharmacology
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• 제16권1호
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• pp.17-24
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• 2012

The hypothalamus-pituitary-adrenocortex (HPA) axis is the central mediator of the stress response. The supramammillary (SuM) region is relatively unique among the hypothalamic structures in that it sends a large, direct projection to the hippocampal formation. It has been shown that mild stress could activate the SuM cells that project to the hippocampus. However, the role of these cell populations in modulating the stress response is not known. The present study examined the effect of stress on different populations of SuM cells that project to the hippocampus by injecting the fluorescent retrograde tracer, fluorogold (FG), into the hippocampus and utilizing the immunohistochemistry of choline acetyltransferase (ChAT), corticotrophin releasing factor (CRF), serotonin (5-HT), glutamate decarboxylase (GAD), tyrosine hydroxylase (TH) and NADPH-d reactivity. Immobilization (IMO) stress (2 hr) produced an increase in the expression of ChAT- immunoreactivity, and tended to increase in CRF, 5-HT, GAD, TH-immunoreactivity and nitric oxide (NO)-reactivity in the SuM cells. Fifty-three percent of 5-HT, 31% of ChAT and 56% of CRF cells were double stained with retrograde cells from the hippocampus. By contrast, a few retrogradely labeled cells projecting to the hippocampus were immunoreactive for dopamine, ${\gamma}$-aminobutyric acid (GABA) and NO. These results suggest that the SuM region contains distinct cell populations that differentially respond to stress. In addition, the findings suggest that serotonergic, cholinergic and corticotropin releasing cells projecting to the hippocampus within the SuM nucleus may play an important role in modulating stress-related behaviors.