• Journal of Life Science
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• v.17 no.3 s.83
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• pp.427-434
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• 2007

Dendritic cells (DCs) play a pivotal roles in the initiation of T cell-mediated immune responses, making them an attractive in immuno vaccines. Angelica gigas and Cnidium officinale were a medicinal herb widely used in Asian countries. In this study, we examined the effects of A. gigas and C. officinale extracts on the DCs functional maturation and phono-type. Immature DCs were cultured in the presence of GM-CSF and IL-4, and the generated immature DCs were stimulated with OVA in the presence or absence A. gigas and C. officinale extracts, respectively, for 24 hours. The antigen-presenting capacity of A. gigas and C. officinale extracts-treated DCs as analyzed by $CD4^+$ helper T cell clone (OVA-specific) proliferation and cytokines (IL-2 and $IFN-{\gamma}$) production were significantly increased. But A. gigas and C. officinale extracts were not directly effected $CD4^+$ helper T cell clone function. Also, the expression of surface co-stimulatory molecules, including major histocompatibility complex (MHC) class II, CD86 and CD11c, is increased on DCs that were stimulated with A. gigas and C. officinale extracts. These results indicate the immunomodulatory properties of A. gigas and C. officinale extracts, which might be medical supplies or health foods.

• Journal of Life Science
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• v.17 no.12
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• pp.1709-1716
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• 2007

The health benefits of garlic (Allium sativum L.) are derived from a wide variety of components and from the different ways it is administered. The known health benefits of garlic include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, protection against microbial, viral and fungal infections, as well as anticancer effects. In the present study, it was examined the effects of water extract of A. sativum (WEAS) on the growth of cultured human tumor cells in order to investigate its anti-proliferative mechanism. Treatment of WEAS to tumor cells resulted in the growth inhibition, especially in leukemia cells, which was associated with induction of G2/M arrest of the cell cycle and apoptosis. In order to further explore the critical events leading to apoptosis in WEAS-treated U937 human leukemia cells, the following effects of WEAS on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 and IAP family proteins. The cytotoxic effect of WEAS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in U937 cells. The WEAS-induced apoptosis in U937 cells was correlated with the generation of intracellular ROS, collapse of MMP, activation of caspase-3 and down-regulation of anti-apoptotic proteins. The quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against WEAS-elicited ROS generation, caspase-3 activation, G2/M arrest and apoptosis. In conclusion, the present study reveals that the cellular ROS generation plays a pivotal role in the initiation of WEAS-triggered apoptotic death in U937 cells.

• Food Science of Animal Resources
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• v.29 no.6
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• pp.659-667
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• 2009

Casein is considered to be the main source of protein in milk; therefore, many studies have been conducted to identify casein-derived bioactive peptides and their physiological effects. Casein is inactive within the parent protein but can be liberated by various proteases and enzymatic hydrolysis during microbial fermentation and gastrointestinal digestion. Once absorbed, casein exhibits different bioavailabilities in the body. Specifically, casein-derived peptides function as angiotensin converting enzyme (ACE) inhibitor in the cardiovascular system; thus, they are expected to reduce and prevent hypertension. Additionally, casein-derived peptides behave as opioid-like peptides in the nervous system, which impacts relaxation. These peptides are also expected to modulate various aspects of immune functions. Finally, caseinophosphopeptide (CPP) and glycomacropeptide (GMP) may exhibit a number of nutritional effects such as the absorption of calcium, iron or zinc. Many studies have been conducted to evaluate casein-derived peptides due to their multifunctional properties and the results of these studies have contributed to the development of a wide variety of functional dairy products. The purpose of this paper was to review the generation of bioactive peptides, their absorption and metabolism, and their specific bioactive effects.

• Journal of Veterinary Science
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• v.22 no.3
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• pp.39.18-39.18
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• 2021

Background: Interferon lambda receptor 1 (IFNLR1) is a type II cytokine receptor that clings to interleukins IL-28A, IL29B, and IL-29 referred to as type III IFNs (IFN-λs). IFN-λs act through the JAK-STAT signaling pathway to exert antiviral effects related to preventing and curing an infection. Although the immune function of IFN-λs in virus invasion has been described, the molecular mechanism of IFNLR1 in that process is unclear. Objectives: The purpose of this study was to elucidate the role of IFNLR1 in the pathogenesis and treatment of porcine reproductive and respiratory syndrome virus (PRRSV). Methods: The effects of IFNLR1 on the proliferation of porcine alveolar macrophages (PAMs) during PRRSV infection were investigated using interference and overexpression methods. Results: In this study, the expressions of the IFNLR1 gene in the liver, large intestine, small intestine, kidney, and lung tissues of Dapulian pigs were significantly higher than those in Landrace pigs. It was determined that porcine IFNLR1 overexpression suppresses PRRSV replication. The qRT-PCR results revealed that overexpression of IFNLR1 upregulated antiviral and IFN-stimulated genes. IFNLR1 overexpression inhibits the proliferation of PAMs and upregulation of p-STAT1. By contrast, knockdown of IFNLR1 expression promotes PAMs proliferation. The G0/G1 phase proportion in IFNLR1-overexpressing cells increased, and the opposite change was observed in IFNLR1-underexpressing cells. After inhibition of the JAK/STAT signaling pathway, the G2/M phase proportion in the IFNLR1-overexpressing cells showed a significant increasing trend. In conclusion, overexpression of IFNLR1 induces activation of the JAK/STAT pathway, thereby inhibiting the proliferation of PAMs infected with PRRSV. Conclusion: Expression of the IFNLR1 gene has an important regulatory role in PRRSV-infected PAMs, indicating it has potential as a molecular target in developing a new strategy for the treatment of PRRSV.

• Journal of Life Science
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• v.31 no.8
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• pp.736-744
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• 2021

Artemisia princeps Pampanini is an herbal medicine widely used to immune function-related diseases, such as anti-oxidative, anti-inflammatory, and antibacterial agents. In this study, we investigated the anti-inflammatory effects of AP extract and underlying mechanisms were evaluated in RAW 264.7 cells. The effects of AP extract were also studied in a complete Freund's adjuvant (CFA)-induced arthritis and lipopolysaccharide (LPS)-induced inflammation mouse model. In RAW 264.7 cells, AP extracts significantly inhibited the LPS-induced nitric oxide (NO) production and inducible NO synthase and cyclooxygenase-2 protein expression. The LPS-induced phosphorylation of mitogen-activated protein kinases and nuclear factor-κB was also significantly blocked by AP extract in RAW 264.7 cells. Oral administration of AP extract suppressed the increase in mouse paw edema and spleen index compared to CFA-treated mice group. Histologically, the infiltration of inflammatory cells was increased in cartilage and synovium in the CFA-treated mouse group, whereas it was suppressed in the AP extract-administered group. Furthermore, AP extract treatment significantly reduced the inflammatory cytokine, tumor necrosis factor-α, levels in CFA and LPS-treated mouse. In conclusion, the anti-inflammatory and anti-arthritis effect of AP extract was confirmed in both in vitro and in vivo models, suggesting that Artemisia princeps Pampanini may be a candidate material for arthritis treatment.

• Journal of Life Science
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• v.31 no.2
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• pp.237-247
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• 2021

Immune responses in the central nervous system (CNS) function as the host's defense system against pathogens and usually help with repair and regeneration. However, chronic and exaggerated neuroinflammation is detrimental and may create neuronal damage in many cases. The NOD-, LRR-, and pyrin domain―containing 3 (NLRP3) inflammasome, a kind of NOD-like receptor, is a cytosolic multiprotein complex that consists of sensors (NLRP3), adaptors (apoptosis-associated speck like protein containing a caspase recruitment domain, ASC) and effectors (caspase 1). It can detect a broad range of microbial pathogens along with foreign and host-derived danger signals, resulting in the assembly and activation of the NLRP3 inflammasome. Upon activation, NLRP3 inflammasome leads to caspase 1-dependent secretion of the pro-inflammatory cytokines IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. NLRP3 inflammasome is highly expressed in CNS-resident cell types, including microglia and astrocytes, and growing evidence suggests that NLRP3 inflammasome is a crucial player in the pathophysiology of several neuroinflammatory and psychiatric diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and major depressive disorder. Thus, this review describes the molecular mechanisms of NLRP3 inflammasome activation and its crucial roles in the pathogenesis of neurological disorders.

• Molecules and Cells
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• v.44 no.1
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• pp.38-49
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• 2021

Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of the gel-forming MUC5AC protein, are significant risk factors for patients with asthma and chronic obstructive pulmonary disease (COPD). The transforming growth factor β (TGFβ) signaling pathway negatively regulates MUC5AC expression; however, the underlying molecular mechanism is not fully understood. Here, we showed that TGFβ significantly reduces the expression of MUC5AC mRNA and its protein in NCI-H292 cells, a human mucoepidermoid carcinoma cell line. This reduced MUC5AC expression was restored by a TGFβ receptor inhibitor (SB431542), but not by the inhibition of NF-κB (BAY11-7082 or Triptolide) or PI3K (LY294002) activities. TGFβ-activated Smad3 dose-dependently bound to MUC5AC promoter. Notably, TGFβ-activated Smad3 recruited HDAC2 and facilitated nuclear translocation of HDAC2, thereby inducing the deacetylation of NF-κB at K310, which is essential for a reduction in NF-κB transcriptional activity. Both TGFβ-induced nuclear translocation of Smad3/HDAC2 and deacetylation of NF-κB at K310 were suppressed by a Smad3 inhibitor (SIS3). These results suggest that the TGFβ-activated Smad3/HDAC2 complex is an essential negative regulator for MUC5AC expression and an epigenetic regulator for NF-κB acetylation. Therefore, these results collectively suggest that modulation of the TGFβ1/Smad3/HDAC2/NF-κB pathway axis can be a promising way to improve lung function as a treatment strategy for asthma and COPD.

• Journal of Life Science
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• v.31 no.5
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• pp.520-526
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• 2021

Microbial protein is one of the sources of protein in the rumen and can also be the source of glutamate production. Glutamic acid is used as fuel in the metabolic reaction in the body and the synthesis of all proteins for muscle and other cell components, and it is essential for proper immune function. Moreover, it is used as a surfactant, buffer, chelating agent, flavor enhancer, and culture medium, as well as in agriculture for such things as growth supplements. Glutamic acid is a substrate in the bioproduction of gamma-aminobutyric acid (GABA). This review provides insights into the role of glutamic acid and glutamic acid-producing microorganisms that contain the glutamate decarboxylase gene. These glutamic acid-producing microorganisms could be used in producing GABA, which has been known to regulate body temperature, increase DM intake and milk production, and improve milk composition. Most of these glutamic acid and GABA-producing microorganisms are lactic acid-producing bacteria (LAB), such as the Lactococcus, Lactobacillus, Enterococcus, and Streptococcus species. Through GABA synthesis, succinate can be produced. With the help of succinate dehydrogenase, propionate, and other metabolites can be produced from succinate. Furthermore, clostridia, such as Clostridium tetanomorphum and anaerobic micrococci, ferment glutamate and form acetate and butyrate during fermentation. Propionate and other metabolites can provide energy through conversion to blood glucose in the liver that is needed for the mammary system to produce lactose and live weight gain. Hence, health status and growth rates in ruminants can be improved through the use of these glutamic acid and/or GABA-producing microorganisms.

• Journal of Life Science
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• v.32 no.7
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• pp.491-500
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• 2022

HK shiitake mushroom mycelium (HKSMM), containing 14% β-glucan, is a health functional food ingredient individually approved by the Korea Ministry of Food and Drug Safety for liver health. The anti-inflammatory effect of a 50% aqueous ethanol extract of HKSMM (designated HKSMM50) was studied in RAW 264.7 macrophage cells treated with lipopolysaccharide (LPS). An active hexose correlated compound (AHCC) was used as a positive control. LPS-activated RAW 264.7 cells were treated with HKSMM50 and AHCC (0, 20, 100, 500 ㎍/ml) and cultured for 24 hr. Inflammation-related elements in the supernatant were measured using enzyme-linked immunosorbent assay (ELISA) kits, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in the cells was analyzed by Western blotting. The HKSMM50 lowered iNOS and COX-2 protein expressions, and nuclear factor-kappa B (NF-κB), nitric oxide (NO) and prostaglandin E₂ (PGE₂) contents in a concentration-dependent manner as compared to LPS treatment. Similarly, the HKSMM50 lowered the content of pro-inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and interleukin-6 (IL-6) contents and increased the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). The efficacy of the AHCC treatment was similar to that of the HKSSM50 treatments. These results indicate that HKSMM50 showed an anti-inflammatory effect in LPS-treated RAW 264.7 cells by down-regulation of NF-κB signaling and suggest that HKSMM could be used as a health functional food ingredient to help improve immune function.

• Herbal Formula Science
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• v.30 no.4
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• pp.241-248
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• 2022

Objective : The purpose of this trial is to observe the preliminary effects of Salvia plebeia (SP) extract on quality of life in patients with solid cancer. Methods : This is a prospective, open-label, single-arm, and single-dose clinical trial. Twenty participants who have been diagnosed with solid cancer between the ages of 20 and 65 will be included. All participants will be administered SP granules for 12 weeks. Data will be collected at 4, 8, and 12 weeks after enrollment. The primary outcome is quality of life, using the Korean version of the Functional Assessment Cancer Therapy-General questionnaire. Secondary outcomes include tumor markers in blood tests for each cancer type, soluble programmed death-ligand 1, the percentage of natural killer cells among lymphocytes, ratio of T-helper and T-suppressor cells, ratio of total T, T-helper, T-suppressor, and B cells in lymphocytes, level of C-reactive protein, and tumor size via radiology examination. Safety will be assessed by clinical laboratory tests and monitoring of adverse events. Discussion : This study aims to observe the effects of an oral administration of SP preparations in patients with solid cancer on changes in quality of life and an improvement in immune function. It is expected to provide objective evidence of the effect and safety of SP for patients with solid cancer. Trial registration: KCT0007315 (Clinical Research Information Service)