• IMMUNE NETWORK
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• v.10 no.6
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• pp.219-229
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• 2010

Background: N-myc downstream regulated gene 2 (NDRG2) is a member of the NDRG gene family. Our previous report indicated a possible role for NDRG2 in regulating the cytokine, interleukin-10 (IL-10), which is an important immunosuppressive cytokine. Several pathways, including p38-MAPK, NF-${\kappa}B$, and JAK/STAT, are used for IL-10 production, and the JAK/STAT pathway can be inhibited in a negative feedback loop by the inducible protein, SOCS3. In the present study, we investigated the effect of NDRG2 gene expression on IL-10 signaling pathway that is modulated via SOCS3 and STAT3. Methods: We generated NDRG2-overexpressing U937 cell line (U937-NDRG2) and treated the cells with PMA to investigate the role of NDRG2 in IL-10 production. U937 cells were also transfected with SOCS3- or NDRG2-specific siRNAs to examine whether the knockdown of SOCS3 or NDRG2 influenced IL-10 expression. Lastly, STAT3 and SOCS3 induction was measured to identify the signaling pathway that was associated with IL-10 production. Results: RT-PCR and ELISA assays showed that IL-10 was increased in U937-mock cells upon stimulation with PMA, but IL-10 was inhibited by overexpression NDRG2. After PMA treatment, STAT3 phosphorylation was decreased in a time-dependent manner in U937-mock cells, whereas it was maintained in U937-NDRG2 cells. SOCS3 was markedly reduced in U937-NDRG2 cells compared with U937-mock cells. IL-10 production after PMA stimulation was reduced in U937 cells when SOCS3 was inhibited, but this effect was less severe when NDRG2 was inhibited. Conclusion: NDRG2 expression modulates SOCS3 and STAT3 activity, eventually leading to the inhibition of IL-10 production.

• 한국균학회소식:학술대회논문집
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• 2014.10a
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• pp.11-11
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• 2014

Fungal pathogens have huge impact on health and economic wellbeing of human by causing life-threatening mycoses in immune-compromised patients or by destroying crop plants. A key determinant of fungal pathogenesis is their ability to undergo developmental change in response to host or environmental factors. Genetic pathways that regulate such morphological transitions and adaptation are therefore extensively studied during the last few decades. Given that epigenetic as well as genetic components play pivotal roles in development of plants and mammals, contribution of microbial epigenetic counterparts to this morphogenetic process is intriguing yet nearly unappreciated question to date. To bridge this gap in our knowledge, we set out to investigate histone modifications among epigenetic mechanisms that possibly regulate fungal adaptation and processes involved in pathogenesis of a model plant pathogenic fungus, Magnaporthe oryzae. M. oryzae is a causal agent of rice blast disease, which destroys 10 to 30% of the rice crop annually. Since the rice is the staple food for more than half of human population, the disease is a major threat to global food security. In addition to the socioeconomic impact of the disease it causes, the fungus is genetically tractable and can undergo well-defined morphological transitions including asexual spore production and appressorium (a specialized infection structure) formation in vitro, making it a model to study fungal development and pathogenicity. For functional and comparative analysis of histone modifications, a web-based database (dbHiMo) was constructed to archive and analyze histone modifying enzymes from eukaryotic species whose genome sequences are available. Histone modifying enzymes were identified applying a search pipeline built upon profile hidden Markov model (HMM) to proteomes. The database incorporates 22,169 histone-modifying enzymes identified from 342 species including 214 fungal, 33 plants, and 77 metazoan species. The dbHiMo provides users with web-based personalized data browsing and analysis tools, supporting comparative and evolutionary genomics. Based on the database entries, functional analysis of genes encoding histone acetyltransferases and histone demethylases is under way. Here I provide examples of such analyses that show how histone acetylation and methylation is implicated in regulating important aspects of fungal pathogenesis. Current analysis of histone modifying enzymes will be followed by ChIP-Seq and RNA-seq experiments to pinpoint the genes that are controlled by particular histone modifications. We anticipate that our work will provide not only the significant advances in our understanding of epigenetic mechanisms operating in microbial eukaryotes but also basis to expand our perspective on regulation of development in fungal pathogens.

• Journal of Life Science
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• v.23 no.10
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• pp.1216-1222
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• 2013

NK cells are lymphoid immune cells that participate in innate immunity to protect against foreign pathogens and transforming cells. It is known that the activity of NK cells is regulated by a balance between activating and inhibitory signals rather than specific antigens. One important activating signal is mediated by the NKG2D receptor, which recognizes NKG2D ligands on cancer cells. Therefore, tumor cells that express sufficient amounts of NKG2D ligands could be eliminated by NKD2D+ cells, including NK cells. Oncogenes drive tumor cells to apoptosis resistant and uncontrolled proliferation by altered expression of many critical genes. Therefore, the expression of NKG2D ligands may be affected by oncogenes. This study focused on increasing the susceptibility of cancer cells to NK cells by regulating the expression of NKG2D ligands influenced by three oncogenes: k-ras, wnt, and c-myc. We demonstrated that inhibition of k-ras and c-myc increased the expression of NKG2D ligands and enhanced the susceptibility of cancer cells to NK cells. On the contrary, inhibition of the wnt pathway decreased MICA and ULBP1 transcripts. Although the decreased transcription of NKG2D ligands by inhibition of the wnt pathway, surface proteins of NKG2D ligands were not changed, and the susceptibility of HCT-116 cells was unaffected. The results demonstrate that the transcription of NKG2D ligands are regulated deferentially by the k-ras, c-myc, and wnt pathways and that the cytotoxicity of NK cells solely depends on the amount of surface NKG2D ligands.

• Journal of Haehwa Medicine
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• v.16 no.2
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• pp.147-169
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• 2007

To evaluate the therapeutic effects of BGG on atopic dermatitis, we investigated the composition of immune cells of lymph node, PBMC and skin of Dermatophagoides farinae-induced NC/Nga mice. The levels of immunoglobulins in serum were analyzed at the protein level and the amount of pathologic cytokines were investigated using CD3/CD28 stimulated splenocytes. The results are summarized below; 1. BGG showed no cytotoxic effect up to $200\;{\mu}g/m{\ell}$ on mLFC in vitro. 2. BGG showed no hepatotoxicity in vivo based on the levels of ALT and AST. 3. Atopic dermatitis was improved through naked eye examination. BGG reduced the skin clinical index from 2.9 to 1.3 (p<0.01). 4. H&E and toluidine blue staining of tissue biopsies revealed that BGG inhibited the infiltration of lymphocytes and mast cells to skin. 5. BGG reduced the number of CD19 positive B cells in PBMCs by 16% (p<0.01), whereas cells were increased by 26% (p<0.05) in lymph nodes. 6. BGG reduced the numbers of B220+/CD23+ cells by 15% (p<0.01) and 33% in PBMCs and lymph node, respectively. 7. BGG reduced the numbers of B220+/IgE+ cells in PBMCs and lymph node by 21% and 33% (p<0.01), respectively. 8. BGG suppressed the levels of IgE (13%, p<0.001) as well as IgM (34%, p<0.001), IgG2a (40%, p<0.001) and IgG2b (26%, p<0.05). 9. BGG reduced the levels of IL-4 and IFN-$\gamma$ by 7% (p<0.05) and 13% (p<0.001) in anti-CD3 and anti-CD28-activated splenocytes, respectively. 10. BGG considerably inhibited the production of TNF-$\alpha$ and IL-6 by 42% (p<0.01) and 15% in the serum, respectively. Based on the results above, we concluded that BGG has therapeutic effects on atopic dermatitis by regulating the differentiation of B cells and isotype switching of IgE. Further investigations on the molecular mechanisms of BGG on atopic dermatitis are anticipated.

• Korean Journal of Medicinal Crop Science
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• v.25 no.5
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• pp.269-281
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• 2017

Background: Small particles increase airway inflammation upon reaching the alveoli. Here, we investigated the protective or therapeutic effects of Salvia plebeia R. Br. (SP_R) extracts on airway inflammation. Methods and Results: To investigate the anti-inflammatory activity of SP_R extracts, we measured their inhibitory effect on the production of reactive oxygen species (ROS) expression of inflammatory mediators, and immune cell infiltration in MH-S alveolar macrophage cells and in the ambient particulate matter (APM)-exposed airway inflammation mice model. The SP_R extracts inhibited the production of ROS and expression of IL-4, IL-10, IL-15, and IL-17A mRNA in APM-stimulated MH-S cells. Oral administration of SP_R extracts suppressed APM-induced inflammatory symptoms, such as high alveolar wall thickness, excess collagen fibers, decreased mRNA expression of chemokines (Ccr9, Ccl5, Ccr3), inflammatory cytokines (IL-15, TNF-${\alpha}$), and IL-4 Th2 cytokine in the lung. The SP_R extracts also inhibited ROS production, granulocyte ($CD11b^+Gr-1^+$) infiltration, IL-17A, TNF-${\alpha}$, macrophage inflammatory protein (Mip-2), and chemokine (C-X-C motif) ligand 1 (Cxcl-1) production in the airway. The specific compounds in the SR-R extracts that mediate the anti-inflammatory effects were identified. Conclusions: In this study, SP_R extracts effectively inhibited airway inflammatory responses, such as ROS production and granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines.

• Journal of the Korean Wood Science and Technology
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• v.41 no.6
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• pp.551-558
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• 2013

Ethanol extracts from Rhododendrom brachycarpum and Abies koreana were investigated for their anti-allergic activities using RBL-2H3 cell line. After treatment with ethanol extracts of various concentrations on the immune response induced mast cell by concanavalin A (Con A), the expressions of cytokine interleukin-4 (IL-4), interleukin-13 (IL-13) were determined by using RT-PCR and the degranulation of mast cells was determined by measuring ${\beta}$-hexosaminidase release. Expression level of IL-4 was decreased by the extract from Rhododendrom brachycarpum in $10^{-7}$, $10^{-5}$ and $10^{-3}%$ concentrations. Expression level of IL-13 was also decreased by both extracts. ${\beta}$-Hexosaminidase release by RBL-2H3 cells was inhibited at the $10^{-5}$ and $10^{-3}%$ concentration of extracts from Rhododendrom brachycarpum and Abies koreana, respectively. These results demonstrate that ethanol extracts of Rhododendron brachycarpum and Abies koreana exert anti-allergic effects by regulating the reduction of IL-4 and IL-13 genes expression and also the secretion of ${\beta}$-hexosaminidase.

• Journal of Life Science
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• v.29 no.7
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• pp.809-816
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• 2019

The ubiquitous plant metabolite p-coumaric acid (p-CA) has antioxidant and anti-inflammatory properties, but its anti-cancer activity has not been established in gastric cancer cell lines. In this study, we investigated the effects of p-CA on the proliferation and transcriptome profile of SNU16 gastric cancer cells. Treatment with p-CA induced apoptosis of the SNU-16 cells by regulating the expression of pro-apoptotic and anti-apoptotic proteins, such as Bcl-2, poly (ADP-ribose) polymerase (PARP), Bax, procaspase-3, and cleaved-caspase-3. The genes differentially expressed in response to p-CA treatment of the SNU-16 cells were identified by RNA sequencing analysis. Genes regulated by p-CA were involved mainly in the inflammatory response, apoptotic processes, cell cycle, and immune response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the phosphatidylinositol-3-kinase-Akt and cancer signaling pathways were altered by p-CA. Protein-protein interaction (PPI) network analysis also revealed that p-CA treatment was correlated with differential expression of genes associated with the inflammatory response and cancer. Collectively, these results suggest that p-CA has potential utility in gastric cancer prevention.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.9
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• pp.211-226
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• 2019

Pig CD45, the leukocyte common antigen, is encoded by the PTPRC gene and CD45 is a T cell-type specific tyrosine phosphatase with alternative splicing of its exons. The CD45 is a coordinated regulator of T cell antigen receptor (TCR) signal transduction achieved by dephosphorylating the phosphotyrosine of its substances, including $CD3{\zeta}$ chain of TCR, Lck, Fyn, and Zap-70 kinase. A dysregulation of CD45 is associated with a multitude of immune disease and has been a target for immuno-drug discovery. To characterize its key structural features with the effects of regulating TCR signaling, this study predicted the unknown structure of pig CD45RO (the smallest isoform) and the complex structure bound to the ITAM (REEpYDV) of $CD3{\zeta}$ chain via homology modeling and docking the peptide, based on the known human CD45 structures. These features were integrated into the structural plasticity of extracellular domains and functional KNRY and PTP signature motifs (the role of a narrow entrance into ITAM binding site) of the tyrosine phosphatase domains in a cytoplasmic region from pig CD45RO. This contributes to the selective recognition of phosphotyrosine from its substrates by adjusting the structural stability and binding affinity of the complex. The characterized features of pigCD45RO can be applied in virtual screening of the T-cell specific immunomodulator.

• Journal of Life Science
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• v.31 no.2
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• pp.183-191
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• 2021

Euglena gracilis is a microalga of great biotechnological interest that can create high levels of bioactive compounds, such as tocopherol, paramylon, and folic acid. The objective of this study was to investigate the biological activities of extracts from E. gracilis, especially those focused on immunological activity. E. gracilis biomass was extracted with hot water (HWE) and the remaining pellet was continuously extracted with methanol (HWME). First, we examined the effect of two extracts from E. gracilis on the production of nitric oxide (NO) and the expression of pro-inflammation cytokines, including IL-1β, IL-6, and TNF-α in murine macrophage RAW 264.7 cells. HWE treatment dose-dependently increased the production of IL-1β and TNF-α. On the other hand, treatment with HWME significantly decreased the generation of NO and pro-inflammatory cytokines (IL-6 and TNF-α) in lipopolysaccharide (LPS)-stimulated macrophage cells. In addition, other biological activities of the extracts were further analyzed: α-glucosidase inhibition, protein tyrosine phosphatase (PTP1B) inhibition, tyrosinase inhibition, xanthine oxidase (XO) inhibition, and angiotensin-converting enzyme (ACE) inhibition. Analysis of these biological activities showed that HWE has more inhibitory effects than HWME against α-glucosidase, tyrosinase, and XO agents. However, the inhibition of PTP1B and ACE with HWME were higher than with HWE. Taken together, the results suggested that E. gracilis possesses various biological activities―especially immunological capabilities―through regulation of cytokine production. Therefore, E. gracilis extract may be potentially useful for food material with immune-regulating effects.

• Journal of Life Science
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• v.31 no.8
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• pp.771-777
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• 2021

Human endogenous retroviruses (HERVs) were inserted into the human genome millions of years ago but they are currently inactive and non-infectious due to recombinations, deletions, and mutations after insertion into the host genome. Nonetheless, recent studies have shown that HERV-derived elements are actually involved in physiological phenomena and certain diseases including cancers. Among the various physiological phenomena related to HERV-derived elements, it is necessary to focus on inflammatory response. HERV-derived elements have been reported to be directly involved in various inflammatory diseases, including autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, amyotrophic lateral sclerosis, and Sjogren's syndrome. As a mechanism for regulating inflammation through HERV-derived elements, the possibility that HERV-derived elements may cause nonspecific innate immune processes and that HERV-derived RNA or proteins may cause selective signaling mechanisms through specific receptors can be considered. However, the mechanism through which HERV-derived elements regulate inflammatory response, such as how silent HERV elements are activated in inflammatory response and what factors and signaling mechanisms are involved in HERV-derived elements, have not been identified to date, making it difficult to study the onset of HERV-related inflammatory disease. In this review, we introduce HERV-related autoimmune diseases and propose the mechanisms of HERV-derived elements at the molecular level of HERV in inflammatory response.