• IMMUNE NETWORK
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• v.19 no.1
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• pp.4.1-4.16
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• 2019

Long noncoding RNAs (lncRNAs) are non-protein coding RNAs of more than 200 nucleotides in length. Despite the term "noncoding", lncRNAs have been reported to be involved in gene expression. Accumulating evidence suggests that lncRNAs play crucial roles in the regulation of immune system and the development of autoimmunity. lncRNAs are expressed in various immune cells including T lymphocytes, B lymphocytes, macrophages, neutrophils, dendritic cells, and NK cells, and are also involved in the differentiation and activation of these immune cells. Here, we review recent studies on the role of lncRNAs in immune regulation and the differential expression of lncRNAs in various autoimmune diseases.

• IMMUNE NETWORK
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• v.12 no.6
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• pp.277-283
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• 2012

Vitamin C is an essential water-soluble nutrient which primarily exerts its effect on host defense mechanisms and immune homeostasis, but the mechanism related to immune-potentiation is poorly understood. Since dendritic cells (DCs) are known as a potent antigen presenting cell (APC) that could enhance the antigen specific immune responses, we investigate the effects of vitamin C on activation of DCs and its related mechanism by using dendritic cell lines, DC-1. First, we found that there was no damage on DC-1 by 2.5 mM of vitamin C. In the presence of vitamin C, the expression of CD80, CD86, and MHC molecules was increased, but it was decreased by the pre-treatment of SB203580, p38 MAPK-specific inhibitor. We confirmed the phosphorylation of p38 MAPK was increased by the treatment of vitamin C. Taken together, these results suggest that vitamin C could enhance the activity of dendritic cells via the up-regulation of the expression of CD80, CD86, and MHC molecules and the activation of p38 MAPK is related to this process.

• IMMUNE NETWORK
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• v.14 no.6
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• pp.307-320
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• 2014

Mycobacterium scrofulaceum is an environmental and slow-growing atypical mycobacterium. Emerging evidence suggests that M. scrofulaceum infection is associated with cervical lymphadenitis in children and pulmonary or systemic infections in immunocompromised adults. However, the nature of host innate immune responses to M. scrofulaceum remains unclear. In this study, we examined the innate immune responses in murine bone marrow-derived macrophages (BMDMs) infected with different M. scrofulaceum strains including ATCC type strains and two clinically isolated strains (rough and smooth types). All three strains resulted in the production of proinflammatory cytokines in BMDMs mediated through toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase 1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor (NF)-${\kappa}B$ together with intracellular reactive oxygen species generation were required for the expression of proinflammatory cytokines in BMDMs. In addition, the rough morphotypes of M. scrofulaceum clinical strains induced higher levels of proinflammatory cytokines, MAPK and NF-${\kappa}B$ activation, and ROS production than other strains. When mice were infected with different M. scrofulaceum strains, those infected with the rough strain showed the greatest hepatosplenomegaly, granulomatous lesions, and immune cell infiltration in the lungs. Notably, the bacterial load was higher in mice infected with rough colonies than in mice infected with ATCC or smooth strains. Collectively, these data indicate that rough M. scrofulaceum induces higher inflammatory responses and virulence than ATCC or smooth strains.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.49 no.5
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• pp.594-599
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• 2016

Infection with HIV (Human immunodeficiency virus), over time, develops into acquired immunodeficiency syndrome (AIDS). The development of non-toxic and effective anti-HIV drugs is one of the most promising strategies for the treatment of AIDS. In this study, we investigated the anti-HIV-1 activity of gelatin hydrolysates from Alaska pollack skin. Gelatin hydrolysates were prepared using four enzymes (alcalase, flavourzyme, neutrase, and pronase E). Among these, the pronase E gelatin hydrolysate was found to inhibit HIV-1 infection in the human T cell-line MT4. It exhibited inhibitory activity on HIV-1_IIIB-induced cell lysis, reverse transcriptase activity, and viral p24 production at noncytotoxic concentrations. Moreover, it decreased the activation of matrix metalloproteinase-2 (MMP-2) in vitro. Because HIV infection-induced activation of MMP-2 can accelerate collagen resolution and collapse of the immune system, pronase E gelatin hydrolysate might prevent the activation of MMP-2 in cells, resulting in collagen stabilization and immune cell homeostasis consistent with anti-HIV activation. These results suggest that pronase E gelatin hydrolysate could potentially be incorporated into a novel therapeutic agent for HIV/AIDS patients.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.172-178
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• 2019

Inflammation is an innate immune response that protects the body from pathogens, toxins, and other dangers and is initiated by recognizing pathogen-associated molecular patterns or danger-associated molecular patterns by pattern-recognition receptors expressing on or in immune cells. Intracellular pattern-recognition receptors, including nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2, and cysteine aspartate-specific protease (caspase)-4/5/11 recognize various pathogen-associated molecular patterns and danger-associated molecular patterns and assemble protein complexes called "inflammasomes." These complexes induce inflammatory responses by activating a downstream effector, caspase-1, leading to gasdermin D-mediated pyroptosis and the secretion of proinflammatory cytokines, such as interleukin $(IL)-1{\beta}$ and IL-18. Ginsenosides are natural steroid glycosides and triterpene saponins found exclusively in the plant genus Panax. Various ginsenosides have been identified, and their abilities to regulate inflammatory responses have been evaluated. These studies have suggested a link between ginsenosides and inflammasome activation in inflammatory responses. Some types of ginsenosides, including Rh1, Rg3, Rb1, compound K, chikusetsu saponin IVa, Rg5, and Rg1, have been clearly demonstrated to inhibit inflammatory responses by suppressing the activation of various inflammasomes, including the NLRP3, NLRP1, and absent in melanoma 2 inflammasomes. Ginsenosides have also been shown to inhibit caspase-1 and to decrease the expression of $IL-1{\beta}$ and IL-18. Given this body of evidence, the functional relationship between ginsenosides and inflammasome activation provides new insight into the understanding of the molecular mechanisms of ginsenoside-mediated antiinflammatory actions. This relationship also has applications regarding the development of antiinflammatory remedies by ginsenoside-mediated targeting of inflammasomes, which could be used to prevent and treat inflammatory diseases.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.47-47
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• 2023

Paeonia lactiflora roots (PLR) are a medicinal plant widely used for treating inflammatory diseases. However, PLR has been recently reported to increase the production of proinflammatory mediators and activates phagocytosis in macrophages. Thus, in this study, we tried to verify the macrophage activation of PLR and elucidate its mechanism of action. PLR upregulated the production of proinflammatory mediators and activated phagocytosis in RAW264.7 cells. However, these effects were reversed by inhibition of TLR2/4. In addition, the inhibition of p38, JNK, and ERK1/2 reduced the PLR-mediated production of proinflammatory mediators, and the PLR-mediated activation of p38, JNK, and ERK1/2 was blocked by the TLR4 inhibition. These findings indicate that PLR may activate macrophages through TLR4-dependent activation of p38, JNK, and ERK1/2. These indicate that PLR has immunostimulatory activity. Thus, it is believed that PLR can be used as a functional food agent that enhances the immune system.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.28 no.4
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• pp.92-110
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• 2015

Objectives : The water extract of Bowon-tang composited with thePanax, AstragalusandGlycyrrhiza Radixhas been traditionally used for treatment of a sickly child and smallpox in oriental medicine. However, little is known about the regulatory effects of Bowon-tang on the production, expression and activity of immune mediators [nitric oxide, prostaglandin E2, inducible nitric oxide synthetase, cyclooxygenase-2], the macrophage activation factor production, the proliferation, subset expression, the killing activity, and the capping in immune cells.Methods : In this study, we investigated the effects of water extracts from Bowon-tang,Panax, AstragalusorGRin mouse immune cells or human Jurkat T cells. Each extract (25-200 ㎍/㎖)perse had no cytotoxic effect in unstimulated macrophages, but concentration-dependently regulated NO and PGE₂production, iNOS expression, and COX-2 activity in mouse peritoneal macrophages with MAF stimulation. These regulatory effects were synergistically increased by their combination (Bowon-tang).Results : The extract of Bowon-tang concentration-dependently regulated T cell proliferation, CD4⁺and CD8⁺expression, and NK killing activity in mouse splenocytes and capping in Jurkat T cells.Conclusions : These results suggest that the water extract of Bowon-tang composited with thePanax, AstragalusandGRmay be useful for therapeutic drugs against a sickly constitution and immune diseases, probably by regulating the production of immune mediators.

• Journal of Periodontal and Implant Science
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• v.26 no.2
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• pp.376-395
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• 1996

The neuropeptide substance P(SP) has been recognized to modulate immune systems, with close proximity between peptidergic sensory nerve endings and immune cells. These include the macrophage and neutrophil activation, IL-2 production in T cell, augmentation of Ig synthesis, mast cell degranulation, $PGE_2$ and collagenase secretion in synoviocytes. In this study I examined SP-induced various biological activities such as antimicrobial action, cytokine production, and mast cell degranulation in the presence or absence of other inflammatory cell activators. Antimicrobial studies showed that undifferentiated HL-60 cells were not affected by SP. However, SP significantly enhanced antimicrobial action of TPA-treated or dbcAMP-treated HL-60 cells which had been differentiated into PMN or macrophage/monocyte. I could not find synergistic relationship between SP and LPS in parallel experiments of the above. SP did not induce IL-l production from murine macrophage cell line RAW264.7 whether costimulated with LPS or not. Mast cell degranulation was occured only when stimulated with high dose ($10^{-5}M$) of SP and the degree of this activation was slightly reduced by simultaneous application of $MIP-1{\alpha}$. In addition, CGRP which is known to be a common coexisting neuropeptide with SP within specific fibers did not augment the function of SP on mast cell degranulation. These results suggest that immunoregulatory activities of SP could be mediated through direct upregulation of various functions of immune cells and also upregulation of responsiveness of immune cells to other immune activators.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.6
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• pp.235-241
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• 2022

The purpose of this study was to investigate the immune activation effect of Sasamsaengmaek-san (SSSMS) consisted of a mixture of Adenophora triphylla var. japonica, Liriope platyphylla, Panax ginseng C. A. Meyer and Schisandra chinensis. in Balb/c mice. Measuring alanine aminotransferase (ALT) and aspartic acid transaminase (AST) levels in Balb/c mice was performed to analyze the cytotoxicity. Cytokines (IFN-γ, IL-2, IL-12) which regulate the immune activation in Balb/c mice were measured by enzyme-linked immunosorbent assay (ELISA). Activated T lymphocytes in peripheral blood mononuclear cell (PBMC), spleen, lymph nodes were analyzed by flow cytometry using percentages. All tests were compared with red ginseng 100 ㎍/mL (RG 100), which is the most used for immune activity. As a result, cytokine activity was significantly increased at SSSMS 300 group. Activated T lymphocytes in PBMC, spleen, lymph nodes were significantly increased at SSSMS 300 group. These results suggest that there is a possibility of SSSMS activating an immune system by activating the cytokines, and it is confirmed that SSSMS also effective for generation and differentiation of T, B lymphocytes which activate the immune response.

• BMB Reports
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• v.48 no.3
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• pp.172-177
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• 2015

Upregulation of pro-inflammatory mediators contributes to ${\beta}$-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic ${\beta}$-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-${\gamma}$. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine-induced signaling cascades leading to nuclear factor kappa B (NF-${\kappa}B$) activation, including $I{\kappa}B$-kinase (IKK) activation, $I{\kappa}B$ degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-${\kappa}B$ in RINm5F cells.