• Journal of Life Science
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• v.33 no.3
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• pp.287-294
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• 2023

Healthy adipose tissue is critical for preventing obesity by maintaining metabolic homeostasis. Adipose tissue plays an important role in energy homeostasis through glucose and lipid metabolism. Depending on nutritional status, adipose tissue expands to store lipids or can be consumed by lipolysis. The role of adipose tissue as an endocrine organ is emerging, and many studies have reported that there are various adipose tissue hormones that communicate with other organs and tissues through metabolic signaling. For example, leptin, a representative peptide hormone secreted from adipose tissues (adipokine), circulates and targets the central nervous system of the brain for appetite regression. Furthermore, adipocytes secrete inflammatory cytokines to target immune cells in adipose tissues. Not surprisingly, adipocytes can secrete fatty acid-derived hormones (lipokine) that bind to their specific receptors for paracrine and endocrine action. To understand organ crosstalk by adipose tissue hor- mones, specific metabolic signaling in adipocytes and other communicating cells should be defined. The dysfunction of metabolic signaling in adipocytes occurs in unhealthy adipose tissue in overweight and obese conditions. Therapy targeting novel adipose metabolic signaling could potentially lead to the development of an effective anti-obesity drug. This review summarizes the latest updates on adipose tissue hormone and metabolic signaling in terms of obesity and metabolic diseases.

• Journal of Life Science
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• v.33 no.2
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• pp.176-182
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• 2023

The stems of Dendrobium moniliforme are used in traditional Oriental medicine as a Yin tonic to nourish the stomach, promote the production of body fluid, and reduce fever. This study investigated the effects of the aqueous extract of D. moniliforme stems (DME) on mast cell degranulation and the expression of tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and histamine-synthesizing enzyme histidine decarboxylase (HDC). We used rat mast cell line RBL-2H3 cells and stimulated them with PMA plus calcium ionophore (PMACI). Pretreatment with DME significantly inhibited PMACI-induced β-hexosaminidase release and the expression of TNF-α, IL-4, and HDC. Furthermore, DME suppressed PMACI-induced nuclear translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). In addition, HDC expression was inhibited by SP600125 (JNK inhibitor), PD98059 (ERK inhibitor), and SB203580 (p38 kinase inhibitor). Finally, the phosphorylation of p38 kinase, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) was inhibited by pretreatment with DME. These results suggest that DME has inhibitory effects against degranulation, cytokine (TNF-α and IL-4) and HDC expression, and that HDC expression is mediated by MAPK signaling. These findings suggest that DME may have therapeutic potential in the treatment of hypersensitive and inflammatory diseases.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.46-46
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• 2003

Interleukin-10 (IL-10) is a homodimeric protein with a wide spectrum of anti-inflammatory and immune activities. It inhibits cytokine production and expression of immune surface molecules in various cell types. The transgenic mice carrying the human IL-10 gene in conjunction with the bovine $\beta$-casein promoter produced the human IL-10 in milk during lactation. Transgenic mice were generated using a standard method as described previously. To screen transgenic mice, PCR was carried out using chromosomal DNA extracted from tail or toe tissues with a primer set. In this study, stability of germ line transmission and expression of IL-10 gene integrated into host chromosome were monitored up to generation F15 of a transgenic line. When female mouse of generation F9 was crossbred with normal male, generation F9 to F15 mice showed similar transmission rates (66.0$\pm$20.13%, 61.5$\pm$16.66%, 41.1$\pm$8.40%, 40.7$\pm$20.34%, 61.3$\pm$10.75%, 49.2$\pm$18.82%, and 43.8$\pm$25.91%, respectively), implying that the IL-10 gene can be transmitted stably up to long term generation in the transgenic mice. For ELISA analysis, IL-10 expression levels were determined with an hIL-10 ELISA and a mIL-10 ELISA kit in accordance with the supplier's protocol. Expression levels of human IL-10 from milk of generation F9 to F13 mice were 3.6$\pm$1.20 mg/ml, 4.2$\pm$0.93 mg/ml, 5.7$\pm$1.46 mg/ml, 6.3$\pm$3.46 mg/ml, and 6.8$\pm$4.52 mg/ml, respectively. These expression levels are higher than in generation F1 (1.6 mg/ml) mice. We concluded that transgenic mice faithfully passed the transgene on their progeny and successively secreted target proteins into their milk through several generations, although there was a little fluctuation in the transmission frequency and expression level between the generations.

• Journal of agriculture & life science
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• v.50 no.2
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• pp.151-160
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• 2016

Inflammatory cytokines play a major role in osteoclastogenesis, leading to the bone resorption that is frequently associated with osteoporosis. Sulforaphane, isolated from the Broccoli(Brassica oleracea var. italia) florets, inhibits the production of inflamatory cytokine. In the present study, we determined inhibitory effect of sulforaphane on Receptor activator of nuclear factor κB ligand(RANKL)-induced osteoclast formation. Sulforaphane inhibited the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase(TRAP), cathepsin K, matrix metalloproteinase 9(MMP-9), and calcitonin receptor in RANKL-induced RAW 264.7 macrophage. Also, sluforaphane inhibited the expression of osteoclast protein, such as TRAP, MMP-9, tumor necrosis factor receptor-associated factor 6(TRAF6) and transcription factor nuclease factor of activated T cells(NFAT)c1. Sulforaphane inhibited RANKL-induced activiation of nuclear factor kappaB(NF-kappaB) by suppression RANKL-mediated NF-kappaB transcriptional acitivation. We are confirmed that sulforaphane inhibits not only transcriptional activity of NF-kappaB but also expressions of the osteoclastogenesis factors(TRAP, cathepsin K, MMP-9, calcitonin, TRAF6) and trranscription factor NFATc1.

• Mood & Emotion
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• v.9 no.3
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• pp.189-193
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• 2011

Objectives : Pro-inflammatory cytokines are related to the pathophysiology of both cancer and depression, and their secretion is controlled by the transcriptional activity of particular gene polymorphisms. This study aimed to investigate whether interleukin (IL)-1β -511C/T gene polymorphism is associated with depression following mastectomy for breast cancer. Methods : A total of 309 patients with breast cancer were evaluated one week after mastectomy, and 244 (79%) were followed one year later. Depression (major+minor depressive disorders) was diagnosed according to DSM-IV criteria using the Mini International Neuropsychiatric Interview, and classified into prevalent, persistent, and incident depression. Associations of IL-1β -511C/T polymorphism with the three depressive status were estimated using logistic regression models. Results : At baseline, 74 (24%) patients were classified with prevalent depression ; and at follow up, 19 (8%) and 25 (10%) patients were classified with persistent and incident depression, respectively. The IL-1β -511T/T genotype was independently associated with prevalent and persistent depression, but not with incident depression. Conclusion : IL-1β -511T/T genotype may involve in the etiology of depression occurring in women with breast cancer who receive a mastectomy.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.82-82
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• 2020

염증 (Inflammation)은 물리적인 상처나 세균감염이 되었을 때 손상된 조직을 재생하고 신체를 방어하기 위해 일어나는 선천성 면역반응으로 알려져 있다. 주로 선천면역을 담당하는 대식세포는 lipopolysaccharide, reactive oxygen species와 cytokine 등에 의해 활성화되어 tumor necrosis factor-α. interleukin-1β, interleukin-6 등 염증인자들의 생성에 관여한다. 특히, 산화질소는 superoxide 음이온과 쉽게 반응하고 peroxynitrite와 같은 독성이 강한 산화제를 생성하여 단백질 및 지질의 과산화를 유도하고 세포독성을 일으키는 것으로 보고되고 있다. 따라서 본 연구에서는 항산화 및 항염증 소재를 탐색하기 위해 오미자 (Schisandra chinensis), 꾸지뽕 (Cudrania tricuspidata)을 이용하여 항산화 활성을 평가하고자 하였으며, 세포주를 활용한 세포독성 및 항염증 활성을 확인하고자 하였다. 본 연구는 전북 순창군에서 재배된 오미자, 꾸지뽕을 열 건조(60℃) 통해 건조한 후 분말화하였다. 최적 추출 조건 선정을 위해 다양한 용매 (열수, 증류수, 주정 20, 40, 60%), 온도 (25, 40, 60, 80℃) 및 시간 (1, 2, 3, 4, 5 h) 조건에서 추출된 추출물의 총 폴리페놀 함량을 비교함으로써 최적 조건을 선정하였다. 오미자와 꾸지뽕의 DPPH 및 ABTS radical 소거 활성, 총 플라보노이드 함량을 확인하여 항산화능 및 기능성 성분 함량을 평가하였다. 또한 대식세포주인 Raw 264.7을 활용하여 MTT assay, 산화질소 생성 억제 활성을 확인하여 세포독성 및 항염증 활성을 평가하였다. 실험 결과, 오미자 및 꾸지뽕은 각각 주정 40%, 60℃ 그리고 증류수, 60℃에서 추출 시 가장 높은 총 폴리페놀 함량 (약 98.3 mg GAE/g 및 88.2 mg GAE/g)을 함유하며, DPPH 라디칼 소거 활성은 약 44.6% 및 24.4%, ABTS 라디칼 소거 활성은 약 30.3% 및 40.8%로 확인되었다. 총 플라보노이드 함량은 약 21.80 mg QE/g 및 35.68 mg QE/g으로 확인되었다. 또한 오미자 및 꾸지뽕 기능성 추출물을 100 ug/mL 처리 시 세포 독성이 나타나지 않는 것으로 확인되었으며, NO 생성량을 약 56.3% 및 21.7% 저감시켜 항염증 효능을 나타내는 것으로 확인되었다.

• Korean Journal of Acupuncture
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• v.41 no.2
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• pp.33-42
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• 2024

Objectives : The sigma-1 receptor is implicated in stress, depression, psychostimulant sensitization, and addiction vulnerability. Prior studies have indicated that ethanol exposure modulates sigma-1 receptor activity within the Ventral Tegmental Area (VTA). Here, we explore the sub-mechanisms underlying sigma-1 receptor activity induced by HT7 (Shinmun) stimulation in behavioral alterations following acute ethanol (ETOH) administration. Methods : Male Wistar rats were investigated for pro- and anti-inflammatory markers after injection of ETOH (1 g/kg) using cytokine enzyme-linked immunosorbent assay (ELISA)s. After confirming that HT7 stimulation changed the total distance traveled in the open field test (OFT), protein changes in the Ventral tegmental area (VTA) were measured by Western blotting. The expression level of inducible nitric oxide synthase (iNOS) after administration of a sigma-1 receptor antagonist (dihydrobromide 1047; BD1047, 10 mg/kg i.p.) and Shenmen (HT7) stimulation was compared. Results : As a result, acute ETOH administration increased proinflammatory marker levels (TNF-𝛼 and IL-6). HT7 stimulation restored the total distance response after acute ethanol administration. In addition, in the VTA, the levels of a microglial marker (iNOS), sigma-1 receptor and protein kinase C, which are predicted to be involved in up- and downregulation, were restored by HT7 stimulation. In particular, HT7 stimulation modulates iNOS expression through effects similar to BD treatment. This study suggests that the stimulatory effect of HT7 may be driven by microglial activation. Conclusions : Microglial activity is regulated by sigma-1 receptor, and sigma-1 receptor activity is regulated by HT7 stimulation. Significantly, we demonstrate that HT7 stimulation ameliorates behavioral alterations induced by acute ETOH administration through microglial activation within the VTA.

• Food Science and Preservation
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• v.30 no.3
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• pp.502-513
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• 2023

This study aimed to evaluate the anti-adipogenic and anti-inflammation effects of extract from Maclura tricuspidata twig fermented with Ganoderma lucidum mycelium (EMFG) in 3T3-L1 preadipocytes. 3T3-L1 adipocytes were treated with 100, 200, 300 ㎍/mL of EMFG. The result showed that EMFG dose-dependently inhibited the accumulation of intracellular lipid content in differentiated 3T3-L1 adipocytes and enhanced increase of adiponectin release and inhibition of leptin release. EMFG treatment reduced expression of adipogenic transcriptional factor such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα). EMFG also decreased production of lipopolysaccharide (LPS)-induced inflammatory cytokine [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1)] and the protein expression of cyclooxygenase-2 (COX-2) and inducible NOS (iNOS) in differentiated 3T3-L1 adipocytes. The study demonstrated that EMFG inhibited adipogenesis and inflammation in a dose-dependent manner. These findings suggest that EMFG may have potential as an anti-obesity and anti-metabolic disease agent that works by inhibiting adipogenesis and inflammation.

• IMMUNE NETWORK
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• v.22 no.3
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• pp.22.1-22.25
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• 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.191-201
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• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.