• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.4
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• pp.36-48
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• 2008

Purpose: The purpose of this study is to investigate anti-inflammatory effect and immune responses of aqueous extract from Fructus Chaenomelis (FC). Methods: We studied anti-inflammatory effect by means of examining the production of NO(nitric oxide) and expressions of pro-inflammatory cytokine (TNF-$\alpha$(tumor necrosis factor-alpha), IL(Interleukin)-6, IL-12) in the LPS-induced peritoneal macrophages of mice. Also, The western blot analysis has been done to look into the mechanism of anti-inflammatory effect. Results: 1. The FC extract did not have any cytotoxicity in the peritoneal macrophages. 2. The FC extract inhibits the productions of NO, IL-6. IL-12 in the LPS-stimulated peritoneal macrophages of mice, but not of TNF-$\alpha$. 3. The FC extract inhibits the activation of NF-${\kappa}B$(nuclear factor-kappa B) by keeping $I{\kappa}B-\alpha$(inhibitory kappa B-alpha) from degradating, but not of MAPKs(mitogen-activated protein kinases) such as ERK(extracelluar signa 1-regulated kinase), JNK(c-Jun N-terminal kinase), p38. Conclusion: These results show that FC extract inhibits the production of pro-inflammatory cytokines such as IL-6. IL-12. NO by inhibiting NF-${\kappa}B$ activation in the peritoneal macrophages of mice. In conclusion, this experiment suggests that FC extract may be effective for the treatment of acute and chronic inflammation including genitourinary infection.

• The Korean Journal of Food And Nutrition
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• v.32 no.2
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• pp.106-113
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• 2019

The objective of this study was to evaluate the effect of fermented Kalopanax pictus (KP-F) on macrophage activation and its effect as a competitive inhibitor of LPS and inhibitory effect on endotoxemia. The results showed that KP-F could activate macrophage in a dose-dependent manner, and KP-F was confirmed to act as a ligand for TLR4. Also, it was found that KP-F did not exhibit the same biotoxicity as LPS in intraperitoneal injection, and that it could suppress the neutrophil migration induced by LPS administration. In normal mice, the body weight, tissue weight, and amount of nitrite and pro-inflammatory cytokines in serum showed no significant changes with KP-F diet for 2 weeks, confirming that administration of KP-F in normal mice did not lead to over activation of immune response and biotoxicity. In the mouse model of endotoxemia induced by LPS and D-galactosamine(D-GalN) in sub-lethal dose, the diet of KP-F effectively inhibited the amount of nitrite and cytokines in the blood, and thus was found to be able to relieve the hepatic and kidney injury. In addition, in the endotoxemia mouse model induced by LPS and D-GalN of lethal dose, the survival rate was increased by KP-F diet in a dose-dependent manner.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1444-1452
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• 2019

The conventional prophylactic vaccines for human papillomavirus (HPV) efficiently prevent infection with high-risk HPV types, but they do not promote therapeutic effects against cervical cancer. Previously, we developed HPV16 E7-expressing Lactobacillus casei (L. casei-E7) as a therapeutic vaccine candidate for cervical cancer, which induces antitumor therapeutic effects in a TC-1 murine cancer model. To improve the therapeutic effect of L. casei-E7, we performed co-treatment with poly-gamma-glutamic acid (${\gamma}-PGA$), a safe and edible biomaterial naturally secreted by Bacillus subtilis. We investigated their synergistic effect to improve antitumor efficacy in a murine cancer model. The treatment with ${\gamma}-PGA$ did not show in vitro cytotoxicity against TC-1 tumor cells; however, an enhanced innate immune response including activation of dendritic cells was observed. Mice co-administered with ${\gamma}-PGA$ and L. casei-E7 showed significantly suppressed growth of TC-1 tumor cells and an increased survival rate in TC-1 mouse models compared to those of mice vaccinated with L. casei-E7 alone. The administration of ${\gamma}-PGA$ markedly enhanced the activation of natural killer (NK) cells but did not increase the E7-specific cytolytic activity of $CD8^+$ T lymphocytes in mice vaccinated with L. casei-E7. Overall, our results suggest that oral administration of ${\gamma}-PGA$ induces a synergistic antitumor effect in combination with L. casei-E7.

• Food Science of Animal Resources
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• v.41 no.5
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• pp.749-762
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• 2021

Colostrum, which contains various immune and growth factors, aids wound healing by promoting keratinocyte proliferation. Aquaporins (AQPs) are small, hydrophobic membrane proteins that regulate cellular water retention. However, few studies have examined the effect of processed colostrum whey on AQP-3 expression in human skin cells. Here, we investigated the effect of milk, colostrum, fermented milk, and fermented colostrum whey on AQP-3 expression in keratinocyte HaCaT cells. Concentrations of 100-400 ㎍/mL of fermented colostrum whey were found to induce HaCaT cell proliferation. AQP-3 was found to be expressed exclusively in HaCaT cells. AQP-3 expression was significantly increased in 100 ㎍/mL fermented colostrum whey-treated cells compared with that in controls. Moreover, fermented colostrum increased p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation, but not ERK1/2 phosphorylation. Thus, our results suggest that fermented colostrum whey increased AQP-3 expression in, and the proliferation of, keratinocytes via JNK and p38 MAPK activation.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.520-528
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• 2022

Mast cells are an effector cell that plays a pivotal role in type I hypersensitive immune responses. Mast cells exist in connective tissues, such as skin and mucosal tissue, and contain granules which contain bioactive substances such as histamine and heparin in cells. The granules of mast cells are secreted by antigen stimulation to cause the type I allergic hypersensitivity. In addition, stimulated by antigen, mast cells synthesize and secrete various eicosanoids and cytokines. While AT9283 is known to have anticancer effects, the therapeutic effect of AT9283 on allergic disorders is completely unknown. In this study, it was found that AT9283 reversibly inhibited antigen-IgE binding-induced degranulation in mast cells (IC₅₀, approx. 0.58 μM) and suppressed the secretion of the inflammatory cytokines IL-4 (IC₅₀, approx. 0.09 μM) and TNF-α (IC₅₀, approx. 0.19 μM). For a mechanism of mast cell inhibition, while not inhibiting Syk phosphorylation, AT9283 suppressed the activation of LAT, a downstream substrate protein of Syk, in a dose-dependent manner. As expected, AT9283 also inhibited the activation of PLCγ1 and Akt, downstream signaling molecules of Syk/LAT, and MAP kinases such as JNK, Erk1/2, and P38. In an in vitro protein tyrosine kinase assay, AT9283 directly inhibited Syk activity. Next, AT9283 dose-dependently inhibited passive cutaneous anaphylaxis (PCA), an IgE-mediated allergic acute response, in mice (ED50, approx. 34 mg/kg, p.o.). These findings suggest that AT9283 has potential to use as a new drug for alleviating the symptoms of IgE-mediated allergic disorders.

• Parasites, Hosts and Diseases
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• v.61 no.2
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• pp.138-146
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• 2023

Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses. Dendritic cells (DCs) are the most prominent type of antigen-presenting cells and regulate the host immune response, including the response of T-cells. However, differences in the DC responses of these mouse strains to T. gondii infection have yet to be characterized. In this study, we cultured bone marrow-derived DCs (BMDCs) from BALB/c and C57BL/6 mice. These cells were infected with T. gondii. The activation of the BMDCs was assessed based on the expression of cell surface markers and cytokines. In the BMDCs of both mouse strains, we detected significant increases in the expression of cell surface T-cell co-stimulatory molecules (major histocompatibility complex (MHC) II, CD40, CD80, and CD86) and cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12p40, IL-1β, and IL-10) from 3 h post-T. gondii infection. The expression of MHC II, CD40, CD80, CD86, IFN-γ, IL-12p40, and IL-1β was significantly higher in the T. gondii-infected BMDCs obtained from the C57BL/6 mice than in those from the BALB/c mice. These findings indicate that differences in the activation status of the BMDCs in the BALB/c and C57BL/6 mice may account for their differential susceptibility to T. gondii.

• IMMUNE NETWORK
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• v.23 no.4
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• pp.34.1-34.15
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• 2023

Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.4
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• pp.323-333
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• 2024

Polychlorinated biphenyls (PCBs) were once used throughout various industries; however, because of their persistence in the environment, exposure remains a global threat to the environment and human health. The Kv1.3 and Kv1.5 channels have been implicated in the immunotoxicity and cardiotoxicity of PCBs, respectively. We determined whether 3,3',4,4'-tetrachlorobiphenyl (PCB77), a dioxin-like PCB, alters human Kv1.3 and Kv1.5 currents using the Xenopus oocyte expression system. Exposure to 10 nM PCB77 for 15 min enhanced the Kv1.3 current by approximately 30.6%, whereas PCB77 did not affect the Kv1.5 current at concentrations up to 10 nM. This increase in the Kv1.3 current was associated with slower activation and inactivation kinetics as well as right-shifting of the steady-state activation curve. Pretreatment with PCB77 significantly suppressed tumor necrosis factor-α and interleukin-10 production in lipopolysaccharide-stimulated Raw264.7 macrophages. Overall, these data suggest that acute exposure to trace concentrations of PCB77 impairs immune function, possibly by enhancing Kv1.3 currents.

• Journal of fish pathology
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• v.26 no.3
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• pp.255-263
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• 2013

The innate immune response is fundamental defense response of vertebrates and invertebrates. Especially, the innate immune response important for larvae that lack of resistance to infectious diseases in the early stages. Galectin is one of the kinds of lectin and presents in the fish mucous that involves innate immune response. Galectin have been studied from various fishing species, but expression analysis of galectin is still unclear during early developmental stage in olive flounder. In this study, we investigated gene expression of galectin-1 from various developmental stage and tissues. We excised several tissues including the muscle, fin, eye, gill, brain, stomach, intestine, kidney, spleen and liver from adult olive flounder and confirmed gene expression of galectin-1 using RT-PCR and quantitative real-time PCR. Expression of galectin-1 was significantly higher in muscle, stomach and intestinal tissue than other tissue in adult fish (5 and 29 months). Also, galectin-1 gene was detected from 0 DAH and gradually increased to 35 DAH and since then decreased after stomach development period. Induction of galectin-1 during the early developmental stage suggest that muscle, fin and eye tissue is formed and begins the secretion of galectin this period. In addition, increased expression levels at 35 DAH suggest that due to complete formation of stomach and intestine, increase of secretion and activation of enzyme. This study shows that expression of galectin-1 during early developmental stages and adult period in olive flounder and can be expect that galectin-1 play essental role in the innate immune system throughout the whole life time. Galectin-1 is primary barrier such as skin and digestive tissue against pathogen infection, also digestive tract developmental period is important for pathogen invasion can be expected that it will serve. Mass mortality due to the disease in seed production is continuing damage, therefore these result will be meaningful about infectious disease during early developmental stages as a basic data for the study.

• Journal of Life Science
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• v.30 no.9
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• pp.826-833
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• 2020

Phospholipase C gamma (PLCγ) has critical roles in receptor tyrosine kinase- and non-receptor tyrosine kinase-mediated cellular signaling relating to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] to produce inositol 1,4,5 trisphosphate (IP₃) and diacylglycerol (DAG), which promote protein kinase C (PKC) and Ca²⁺ signaling to their downstream cellular targets. PLCγ has two isozymes called PLCγ1 and PLCγ2, which control cell growth and differentiation. In addition to catalytically active X- and Y-domains, both isotypes contain two Src homology 2 (SH2) domains and an SH3 domain for protein-protein interaction when the cells are activated by ligand stimulation. PLCγ also contains two pleckstrin homology (PH) domains for membrane-associated phosphoinositide binding and protein-protein interactions. While PLCγ1 is widely expressed and appears to regulate intracellular signaling in many tissues, PLCγ2 expression is restricted to cells of hematopoietic systems and seems to play a role in the regulation of immune response. A distinct mechanism for PLCγ activation is linked to an increase in phosphorylation of specific tyrosine residue, Y783. Recent studies have demonstrated that PLCγ mutations are closely related to cancer, immune disease, and brain disorders. Our review focused on the physiological roles of PLCγ by means of its structure and enzyme activity and the pathological functions of PLCγ via mutational analysis obtained from various human diseases and PLCγ knockout mice.