Lee, Su Jung;Shin, Sung Jae;Lee, Seung Jun;Lee, Moon Hee;Kang, Tae Heung;Noh, Kyung Tae;Shin, Yong Kyoo;Kim, Han Wool;Yun, Cheol-Heui;Jung, In Duk;Park, Yeong-Min
BMB Reports
/
v.47
no.9
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pp.512-517
/
2014
In this study, we showed that Mycobacterium abscessus MAB2560 induces the maturation of dendritic cells (DCs), which are representative antigen-presenting cells (APCs). M. abscessus MAB2560 stimulate the production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-${\alpha}$, IL-$1{\beta}$, and IL-12p70] and reduce the endocytic capacity and maturation of DCs. Using $TLR4^{-/-}$ DCs, we found that MAB2560 mediated DC maturation via Toll-like receptor 4 (TLR4). MAB2560 also activated the MAPK signaling pathway, which was essential for DC maturation. Furthermore, MAB2560-treated DCs induced the transformation of $na\ddot{i}ve$ T cells to polarized $CD4^+$ and $CD8^+$ T cells, which would be crucial for Th1 polarization of the immune response. Taken together, our results indicate that MAB2560 could potentially regulate the host immune response to M. abscessus and may have critical implications for the manipulation of DC functions for developing DC-based immunotherapy.
Expressed sequence tag (EST) analysis was conducted using a complementary DNA (cDNA) library made from the kidney mRNA of olive flounder (Paralichthys olivaceus). In the survey of 390 ESTs chosen from the kidney cDNA library, 250 ESTs showed significant homology to previously described genes while 140 ESTs were unidentified or novel. Comparative analysis of the 250 identified ESTs showed that 14 (5.6%) clones were representing 11 unique genes identified as homologous to the previously reported olive flounder ESTs, 198 (79.2%) clones representing 160 unique genes were identified as orthologs of known genes from other organisms, and orthologs were established for 38 (15.2%) clones representing 37 genes of known sequences with unknown functions. We also identified several kinds of immune associated proteins, indicating EST as a powerful method for identifying immunerelated genes of fish as well as identifying novel genes. Further studies using cDNA microarrays are needed to identify the differentially expressed transcripts after disease infection.
Jayaramayya, Kaavya;Mahalaxmi, Iyer;Subramaniam, Mohana Devi;Raj, Neethu;Dayem, Ahmed Abdal;Lim, Kyung Min;Kim, Se Jong;An, Jong Yub;Lee, Yoonjoo;Choi, Yujin;Kirubhakaran, Arthi;Cho, Ssang-Goo;Vellingiri, Balachandar
BMB Reports
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v.53
no.8
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pp.400-412
/
2020
The world has witnessed unimaginable damage from the coronavirus disease-19 (COVID-19) pandemic. Because the pandemic is growing rapidly, it is important to consider diverse treatment options to effectively treat people worldwide. Since the immune system is at the hub of the infection, it is essential to regulate the dynamic balance in order to prevent the overexaggerated immune responses that subsequently result in multiorgan damage. The use of stem cells as treatment options has gained tremendous momentum in the past decade. The revolutionary measures in science have brought to the world mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exo) as therapeutic opportunities for various diseases. The MSCs and MSC-Exos have immunomodulatory functions; they can be used as therapy to strike a balance in the immune cells of patients with COVID-19. In this review, we discuss the basics of the cytokine storm in COVID-19, MSCs, and MSC-derived exosomes and the potential and stem-cell-based ongoing clinical trials for COVID-19.
Background: Variants of human papillomavirus (HPV) show more oncogenicity than do prototypes. The HPV16 Asian variant (HPV16As) plays a major role in cervical cancer of Asian populations. Some amino acid changes in the E6 protein of HPV16 variants affect E6 functions such as p53 interaction and host immune surveillance. This study aimed to investigate activities of HPV16As E6 protein on modulation of expression of miRNA-21 as well as interferon regulatory factors (IRFs) 1, 3, 7 and c-fos. Materials and Methods: Vectors expressing E6 protein of HPV16As (E6D25E) or HPV16 prototype (E6Pro) were constructed and transfected into C33A cells. HCK1T cells expressing E6D25E or E6Pro were established by transducing retrovirus-containing E6D25E or 16E6Pro. The E6AP-binding activity of E6 and proliferation of the transfected C33A cells were determined. MiR-21 and mRNA of interesting genes were detected in the transfected C33A cells and/or the HCK1T cells, with or without treatment by culture medium from HeLa cells (HeLa-CM). Results: E6D25E showed binding activity with E6AP similar to that of E6Pro. Interestingly, E6D25E showed a higher activity of miR-21 induction than did E6Pro in C33A cells expressing E6 protein. This result was similar to the HCK1T cells expressing E6 protein, with HeLa-CM treatment. The miR-21 up-regulation significantly corresponded to its target expression. Different levels of expression of IRFs were also observed in the HCK1T cells expressing E6 protein. Interestingly, when treated with HeLa-CM, IRFs 1, 3 and 7 as well as c-fos were significantly suppressed in the HCK1T cells expressing E6D25E, whereas those in the HCK1T cells expressing E6Pro were induced. A similar situation was seen for IFN-${\alpha}$ and IFN-${\beta}$. Conclusions: E6D25E of the HPV16As variant differed from the E6 prototype in its activities on epigenetic modulation and immune surveillance and this might be a key factor for the important role of this variant in cervical cancer progression.
Glial cells such as astrocytes and microglial cells are the main source of proinflammatory cytokines and nitric oxide(NO) in the central nervous system, which exert neuroimmune and inflammatory functions and other various neurobiologic effects. Though Panax ginseng C.A. Meyer has been known to strengthen the body's defence mechanisms and also to maintain the homeostasis in the central nervous system, the effects of Panax ginseng on the production of immune and inflammatory mediators have not been studied well in the brain. Therefore, this study was designed to study the effects of ginseng saponins on the production of proinflammatory cytokines and NO in the primary cultures of mixed glial cells. White ginseng saponin, 200-500 $\mu$g/ml, showed significant cytotoxicity after 72 hrs and increased TNF-$\alpha$, IL-$\beta$, and NO production. Lower doses of 50-100 $\mu\textrm{g}$/ml showed little cytotoxicity until 72 hrs and also increased the production of TNF-$\alpha$, IL-1$\beta$, and NO. Triple immune staining showed that white ginseng saponin, 200$\mu\textrm{g}$/ml for 72 ks, induced stellation of astrocytes and iNOS expression exclusively in microglial cells. Taken together, the white ginseng saponin increased the production of proinflammatory cytokines such as TNF-$\alpha$ and IL-1$\beta$, and induced iNOS expression and NO production in mixed glial cell cultures, which may be ascribed to the enhancement of central immune responses and the regulation of inflammatory reactions by Panax ginseng.
Hemocyte parameters of the wild Pacific oyster Crassostrea gigas inhabiting intertidal zones in small bays (Gwangyang and Jinhae Bay) on the southern coast of Korea were evaluated using flow cytometry and neutral red retention (NRR) assay. Morphological features, cell count, mortality, DNA damage, phagocytosis, and lysosomal membrane stability of hemocytes were analyzed. Three types of hemocytes were identified in the oyster hemolymph: granulocytes, hyalinocytes, and blast-like cells. Immune related functions of hemocyte including phagocytosis and lysosomal membrane stability were significantly different among the study areas (P<0.05), while cell count, mortality, and DNA damage of hemocytes were not significantly different. In Gwangyang Bay, phagocytosis of granulocytes and lysosomal membrane stability of oyster hemocytes inhabiting inside bay were significantly lower than those of oyster hemocytes in outside bay (P<0.05), indicating that oysters in inside bay of Gwangyang were relatively suppressed the immunological function in hemocytes. Contrary to Gwangyang Bay, immune parameters of oyster hemocytes in Jinhae Bay not showed the difference between sampling sites. In conclusion, flow cytometry and NRR assay using oyster hemocyte has a powerful tool to investigate the cell level in a short time due to no-preprocessing of material.
The purpose of this study was to test the effectiveness of self-management relaxation training through biofeedback and progressive muscle relaxation methods. The effectiveness of the experimental methods was tested by measuring the degree of symptoms of stress (SOS), the McNair's profile of Mood States (POMS), the levels of ephinephrine, norepinephrine, pulse rate, blood pressure and natural killer cells. The subjects of this study were sixty six nursing students divided into four groups : two groups were the biofeedback and progressive muscle relaxation groups, the other two groups served as control groups. One was a group of sophomores with no experience at all, the other a junior group without self -management or relaxation training. This study was conducted for eight weeks of clinical practice from April, 26th 1998 to June, 20th 1998. Biofeedback training was done with software developed by J&J company (1-410 form for abdominal respiration training). Progressive muscle relaxation training was done with u audiotape recorded according to Jacobson's Theory. The data were analyzed with frequencies, means, and analysis of covariance using the SPSS program and the significance level of statistics was 5%. The results of the study are : 1) The importance of clinical practice stress reduction is shown in that the level of symptoms of stress in the experimental groups in clinical practice was higher than in the group receiving only a lecture. 2) The relaxation training methods of biofeedback and progressive muscle relaxation were effective in reducing the symptoms of stress under the clinical practice stress conditions. 3) The effectiveness of the biofeedback training relaxation method to reduce symptoms of stress was higher than that of progressive muscle relaxation. 4) The relaxation training methods of biofeedback and progressive muscle relaxation were effective in reducing stressful mood states. 5) The relaxation training methods of biofeedback and progressive muscle relaxation were not effective in reducing epinephrine and norepinephrine levels. 6) The relaxation training methods of biofeedback and progressive muscle relaxation were effective in increaing the number of natural killer cells. 7) The relaxation training methods of biofeedback and progressive muscle relaxation were effective in decreasing high systolic and diastolic values of blood pressure and high pulse rates. In summary, the relaxation methods of biofeedback and progressive muscle relaxation in reducing clinical practice stress were effective in lowering the level of symptoms of stress and the profile of stressful mood states. They were also effective in lowering high blood pressure and pulse rates. The relaxation methods were effective in increasing the number of natural killer cells as part of the immune function. However, relaxation methods were not effective in reducing the catecholamine level. The biofeedback training method for reduction of symptoms of stress was more effective than the progressive muscle relaxation method.
Toll-like receptors (TLRs) can recognize conserved molecular patterns and initiate a wide range of innate and adaptive immune responses against invading infectious agents. The aim of this study was to assess the transcript profile of mink TLRs (mTLRs) in mink peripheral blood mononuclear cells (PBMCs) and a range of tissues, and to explore the potential role of mTLRs in the antiviral immune response process. The results indicated that the mTLR partial nucleotide sequences had a high degree of nucleotide identity with ferret sequences (95-98%). Phylogenetic analysis showed that mammalian TLRs grouped into five TLR families, with a closer relationship of the mTLRs with those of ferret than the other mammalian sequences. Moreover, all the mTLRs were ubiquitously expressed in lymphoid organs (spleen and lymph nodes) and PBMCs. Interestingly, the mTLR expression patterns in lung, uterus, and heart showed quite a lot of similarity. Another remarkable observation was the wide expression of mTLR1-3 mRNAs in all tissues. Among the analyzed tissues, skeletal muscle was revealed to being the lowest repertoire of mTLR expression. Additionally, mink PBMCs exposed to the canine distemper virus revealed significant upregulation of mTLR2, mTLR4, mTLR7, and mTLR8 mRNAs, indicating that mTLRs have a role in innate immunity in the mink. Collectively, our results are the first to establish the basic expression patterns of mTLRs and the relationship between mTLRs and a virus, which will contribute to better understanding of the evolution and the functions of mTLRs in the innate immune system in minks.
Objectives : Regulatory T cells can reduce inflammation and allergic reactions through their inhibitory functions. Gardeniae Fructus(GF) is a Heat-clearing herb used in traditional Korean medicine, and a wide range of studies on its antiinflammatory effects are being carried out. The authors investigated the effect that Gardeniae Fructus has on regulatory T cells. Methods : The authors screened 14 herbs for their effects on regulatory T cells. 100mg of each herb were separately dissolved in 1ml of sterile saline and the supernatant was harvested after 10 minutes of centrifuge at 15,000 rpm. The supernatant was filtered through a 0.2 ${\mu}m$ syringe filter, and the resulting stock was refrigerated at $4^{\circ}C$. The stock was diluted before testing and used at a final concentration of $0.01{\mu}g/ml$. CD4+CD25+ T cells from healthy BALB/c spleens were used as natural regulatory T cells (nTreg), and CD4+CD25- T cells were used as reactive T cells. CD4+CD25+ and CD4+CD25- T cells were activated with anti-CD3e ($10{\mu}g/m{\ell}$)/anti-CD28 ($1{\mu}g/m{\ell}$) and cultured. IL-10 from supernatant of the culture medium was measured by IL-10 cytokine ELISA. The percentages, cell numbers, phenotype and function of CD4+CD25+ Treg cells were determined by flow cytometry. Results : Gardeniae Fructus was shown to be the most potent herb among the 14 herbs tested for suppressing CD4+CD25- reactive T cell proliferation by stimulating CD4+CD25+ natural regulatory T cells. Gardeniae Fructus induces IL-10 secretion increase by stimulating CD4+CD25+ natural regulatory T cells, and indirectly suppresses CD4+CD25- reactive T cell proliferation through increasing CD25 (IL-2 receptor $\alpha$) expression and thus promoting bonding with IL-2. Gardeniae Fructus did not directly affect CD4+CD25- reactive T cell proliferation. Conclusions : Gardeniae Fructus suppressed reactive T cell proliferation through inducing increases in IL-10 secretion and CD25 (IL-2 receptor $\alpha$) expression.
The maintenance of peripheral immune tolerance and prevention of chronic inflammation and autoimmune disease require $CD4^{+}CD25^{+}$ T cells (regulatory T cells). The transcription factor Foxp3 is essential for the development of functional, regulatory T cells, which plays a prominent role in self-tolerance. Retroviral vectors can confer high level of gene transfer and transgene expression in a variety of cell types. Here we observed that following retroviral vector-mediated gene transfer of Foxp3, transductional Foxp3 expression was increased in the liver, lung, brain, heart, muscle, spinal cord, kidney and spleen. One day after vector administration, high levels of transgene and gene expression were observed in liver and lung. At 2 days after injection, transductional Foxp3 expression level was increased in brain, heart, muscle and spinal cord, but kidney and spleen exhibited a consistent low level. This finding was inconsistent with the increase in both $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell frequencies observed in peripheral immune cells by fluorescence-activated cell-sorting (FACS) analysis. Retroviral vector-mediated gene transfer of Foxp3 did not lead to increased numbers of $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell. These results demonstrate the level and duration of transductional Foxp3 gene expression in various tissues. A better understanding of Foxp3 regulation can be useful in dissecting the cause of regulatory T cells dysfunction in several autoimmune diseases and raise the possibility of enhancing suppressive functions of regulatory T cells for therapeutic purposes.
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