• IMMUNE NETWORK
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• 제23권3호
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• pp.22.1-22.15
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• 2023

Alcoholic liver cirrhosis (ALC) is caused by chronic alcohol overconsumption and might be linked to dysregulated immune responses in the gut-liver axis. However, there is a lack of comprehensive research on levels and functions of innate lymphocytes including mucosal-associated invariant T (MAIT) cells, NKT cells, and NK (NK) cells in ALC patients. Thus, the aim of this study was to examine the levels and function of these cells, evaluate their clinical relevance, and explore their immunologic roles in the pathogenesis of ALC. Peripheral blood samples from ALC patients (n = 31) and healthy controls (HCs, n = 31) were collected. MAIT cells, NKT cells, NK cells, cytokines, CD69, PD-1, and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. Percentages and numbers of circulating MAIT cells, NKT cells, and NK cells were significantly reduced in ALC patients than in HCs. MAIT cell exhibited increased production of IL-17 and expression levels of CD69, PD-1, and LAG-3. NKT cells displayed decreased production of IFN-γ and IL-4. NK cells showed elevated CD69 expression. Absolute MAIT cell levels were positively correlated with lymphocyte count but negatively correlated with C-reactive protein. In addition, NKT cell levels were negatively correlated with hemoglobin levels. Furthermore, log-transformed absolute MAIT cell levels were negatively correlated with the Age, Bilirubin, INR, and Creatinine score. This study demonstrates that circulating MAIT cells, NKT cells, and NK cells are numerically deficient in ALC patients, and the degree of cytokine production and activation status also changed. Besides, some of their deficiencies are related to several clinical parameters. These findings provide important information about immune responses of ALC patients.

• BMB Reports
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• 제55권2호
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• pp.81-86
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• 2022

Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

• IMMUNE NETWORK
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• 제21권6호
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• pp.43.1-43.14
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• 2021

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4⁺ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22⁺ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22⁺ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22⁺ ILC3, NKp44^- ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP⁺ cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22⁺ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22⁺ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.

• IMMUNE NETWORK
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• 제11권6호
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• pp.376-382
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• 2011

Background: Carbon monoxide (CO) is a cytoprotective and homeostatic molecule with important signaling capabilities in physiological and pathophysiological situations. CO protects cells/tissues from damage by free radicals or oxidative stress. NAD(P)H:quinone oxidoreductase (NQO1) is a highly inducible enzyme that is regulated by the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway, which is central to efficient detoxification of reactive metabolites and reactive oxygen species (ROS). Methods: We generated NQO1 promoter construct. HepG2 cells were treated with CO Releasing Molecules-2 (CORM-2) or CO gas and the gene expressions were measured by RT-PCR, immunoblot, and luciferase assays. Results: CO induced expression of NQO1 in human hepatocarcinoma cell lines by activation of Nrf2. Exposure of HepG2 cells to CO resulted in significant induction of NQO1 in dose- and time-dependent manners. Analysis of the NQO1 promoter indicated that an antioxidant responsible element (ARE)-containing region was critical for the CO-induced Nrf2-dependent increase of NQO1 gene expression in HepG2 cells. Conclusion: Our results suggest that CO-induced Nrf2 increases the expression of NQO1 which is well known to detoxify reactive metabolites and ROS.

• 대한임상검사과학회지
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• 제55권2호
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• pp.105-112
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• 2023

Leucine-rich repeat kinase 2 (LRRK2)는 파킨슨병과 같은 신경퇴행성 질환의 병태생리학적인 측면에서 중요한 역할을 하는 것으로 알려져 있고 주로 뇌뿐만 아니라 폐에서도 발현된다. 그러나 LRRK2 발현이 폐 편평세포암(lung squamous cell carcinoma, LUSC)과 같은 일반적인 폐암의 아형과 병인성이 있는지는 불분명하다. 본 연구에서는 Kaplan Meier 플로터 생물정보학 온라인 도구를 사용하여 폐 편평세포암종 내에서 LRRK2와의 예후 진단가치를 분석하였다. 폐 편평세포암종 환자는 LRRK2의 발현이 높아지면 더 나쁜 예후를 나타낸다고 알려져 왔다. LRRK2 발현이 높은 환자의 경우 종양 돌연변이 부담, 높은 신항원부하, 더 나쁜 생존율, 성별과 상관관계를 보였다. 더욱이, gene expression profiling interactive analysis 데이터분석에서 높은 LRRK2 발현을 가진 환자에서의 심각한 증상은 항염증성 사이토카인(예, IL-4, IL-10)의 높은 발현에 양의 상관관계를 보였지만 염증성 사이토카인은 상관성이 없었다. 이러한 결과에서 IL-10관련 유전자의 높은 발현은 더 나쁜 예후를 보이는 LRRK2-high 환자들에서 유의미하게 연관성을 보였다. 또한, tumor immunity estimation resource 데이터는 큰포식세포가 LRRK2-high LUSC환자에서 IL-10의 기원세포 중 하나임을 보여주었다. 본 연구를 통해 결과적으로 LRRK2-IL10 축의 가설이 LUSC 환자의 잠재적이 치료 표적과 예후 바이오 마커일 수 있음을 보여주었다.

• 한국해양바이오학회지
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• 제15권2호
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• pp.33-40
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• 2023

This study aimed to investigate the immunomodulatory function of Pyropia yezoensis hydrothermal (water) extract (PYWE) in comparison to the group treated only with lipopolysaccharides (LPS) in RAW264.7 cells. LPS is known to be an inflammatory mediator that activates macrophages, leading to the secretion of nitric oxide (NO), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) as defense responses. Through enzyme-linked immunoassay and western blot analyses, it was observed that PYWE increased the expression levels of NO, iNOS, TNF-α, and IL-6 in RAW264.7 cells in a dose-dependent manner, although to a lesser extent compared with the group treated with LPS alone. In addition, the study examined the mitogen-activated protein kinases (MAPKs) pathway, which regulates various cellular activities, including gene expression, mitosis, cell differentiation, transformation, survival, and death. The western blot analysis confirmed that PYWE also regulated the MAPKs pathway. Furthermore, the expression levels of immunomodulatory-related factors increased in the group treated with PYWE compared with the control group. Even though the effects of PYWE were usually less strong than those of LPS, the effects of PYWE increased with increasing doses compared to the control group. This suggests that PYWE could be used to control the immune system.

• Journal of Plant Biotechnology
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• 제45권4호
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• pp.306-314
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• 2018

Korean ginseng (Panax ginseng) has long been cultivated as an important economic medicinal plant. Owing to the seasonal and long-term agricultural cultivation methods of Korean ginseng, they are always vulnerable to various environmental stress conditions. ABSCISIC ACID (ABA) is an essential plant hormone associated with seed development and diverse abiotic stress responses including drought, cold and salinity stress. By modulating ABA responses, plants can regulate their immune responses and growth patterns to increase their ability to tolerate stress. With recent advances in genome sequencing technology, we first reported the functional features of genes related to canonical ABA signaling pathway in P. ginseng genome. Based on the protein sequences and functional genomic analysis of Arabidopsis thaliana, the ABA related genes were successfully identified. Our functional genomic characterizations clearly showed that the ABA signaling related genes consisting the ABA receptor proteins (PgPYLs), kinase family (PgSnRKs) and transcription factors (PgABFs, PgABI3s and PgABI5s) were evolutionary conserved in the P. ginseng genome. We confirmed that overexpressing ABA related genes of P. ginseng completely restored the ABA responses and stress tolerance in ABA defective Arabidopsis mutants. Finally, tissue and age specific spatio-temporal expression patterns of the identified ABA-related genes in P. ginseng tissues were also classified using various available RNA sequencing data. This study provides ABA signal transduction related genes and their functional genomic information related to the growth and development of Korean ginseng. Additionally, the results of this study could be useful in the breeding or artificial selection of ginseng which is resistant to various stresses.

• IMMUNE NETWORK
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• 제2권4호
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• pp.217-222
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• 2002

Background: Scid.adh is a recently developed murine thymic lymphoma cell line, which has been used as in vitro model for the study of double negative stage III thymocytes. In this study, we compared the expression profile of a number of genes and proteins, which are tightly related to T cell development and apoptosis, in thymic lymphoma cell lines, R1.1, EL-4, and Scid.adh for the developmental staging. Methods: We examined the expression of development marker genes and proteins in three lymphoma cell lines by flow cytometry and RT-PCR. In addition, the expression of apoptosis-related molecules including bcl-2, bax and Fas was also investigated. Results: As previously reported, Scid.adh cell line expressed CD8 and CD25 but not TCR ${\alpha}$ chain, while R1.1 cells expressed TCR ${\alpha}$ chain and both CD4 and CD8 transcripts. These suggest that R1.1 might be in double positive stage, and low level of CD44 expression and the absence of CD25 support this suggestion. In contrast, EL-4 cells showed high level of TCR ${\alpha}$ chain transcript, and low-level of CD4 expression, suggesting that EL-4 is in more mature stage than R1.1. Further, this suggestion was supported by the lack of mT-20 in EL-4 cells, which is expressed in the immature thymocytes, and Scid.adh and R1.1 cell lines, but not in the terminally differentiated thymocytes and peripheral T cells. Among the apoptosis-related gene, transcripts of bcl-2 gene were detected in both R1.1 and EL-4 but not in Scid.adh cells, while bax was expressed in all cell lines. Fas expression was the highest in EL-4 cells and low in Scid.adh cell line. Conclusion: R1.1 cell may represent double positive stage, and EL-4 is more differentiated cell line. In addition, Scid.adh and EL-4 cell lines are suspected to be useful for the study of function of bcl-2 family and Fas during the thymocyte development, respectively.

• Journal of Microbiology and Biotechnology
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• 제34권5호
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• pp.1109-1118
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• 2024

Probiotics, specifically Lacticaseibacillus rhamnosus, have garnered attention for their potential health benefits. This study focuses on evaluating the probiotic properties of candidate probiotics L. rhamnosus IDCC 3201 (3201) using the Caenorhabditis elegans surrogate animal model, a well-established in vivo system for studying host-bacteria interactions. The adhesive ability to the host's gastrointestinal tract is a crucial criterion for selecting potential probiotic bacteria. Our findings demonstrated that 3201 exhibits significantly higher adhesive capabilities compared with Escherichia coli OP50 (OP50), a standard laboratory food source for C. elegans and is comparable with the widely recognized probiotic L. rhamnosus GG (LGG). In lifespan assay, 3201 significantly increased the longevity of C. elegans compared with OP50. In addition, preconditioning with 3201 enhanced C. elegans immune response against four different foodborne pathogenic bacteria. To uncover the molecular basis of these effects, transcriptome analysis elucidated that 3201 modulates specific gene expression related to the innate immune response in C. elegans. C-type lectin-related genes and lysozyme-related genes, crucial components of the immune system, showed significant upregulation after feeding 3201 compared with OP50. These results suggested that preconditioning with 3201 may enhance the immune response against pathogens. Metabolome analysis revealed increased levels of fumaric acid and succinic acid, metabolites of the citric acid cycle, in C. elegans fed with 3201 compared with OP50. Furthermore, there was an increase in the levels of lactic acid, a well-known antimicrobial compound. This rise in lactic acid levels may have contributed to the robust defense mechanisms against pathogens. In conclusion, this study demonstrated the probiotic properties of the candidate probiotic L. rhamnosus IDCC 3201 by using multi-omics analysis.

• 동의생리병리학회지
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• 제18권2호
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• pp.468-473
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• 2004

Psoriasis is a chronic inflammatory disease of the skin characterized by epidermal hyperplasia, dermal angiogenesis, infiltration of activated T cells, and increased cytokine levels, and affects 1-3% of the world-wide population. Although many immunological and clinical reports indicate a role for the immune system in the pathogenesis of psoriasis, puzzling questions about psoriasis remain unsolved. During the several decade, immunosuppressor and PUVA treatment are ubiquitously used to psoriasis therapy. But recently, to promote terminal differentiation of keratinocytes, block either NK-Tcell or T-cell activation, and interrupting the angiogenic switch represent another therapeutic opportunity in psoriasis. To keep face with immunological therapy, the needs of newly designed prescription on the psoriasis treatments were demanded. With the object of understand the psoriasis from an orient medical point of view, patients were administrated the GY during several weeks. We investigated the changes of gene expression in involved and uninvolved skin samples during the oriental remedy. Microarray data showed several important results. First, Gene expression profiling is similar to each patient. Second, precursor proteins that organize cornified envelops are decreased at the end of remedy. But genes which related to apoptosis, G-protein signalling, and lipid metabolism are increased. Third, 68.5% of clustering genes localized on the psoriasis susceptibility locus. In our results indicated that GY influence on the keratinocytes hyperproliferation by regulating the gene, which located on the psoriasis susceptibility locus.