• BMB Reports
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• v.50 no.12
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• pp.640-646
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• 2017

Regulatory B cells, also well-known as IL-10-producing B cells, play a role in the suppression of inflammatory responses. However, the epigenetic modulation of regulatory B cells is largely unknown. Recent studies showed that the bromodomain and extra-terminal domain (BET) protein inhibitor JQ1 controls the expression of various genes involving cell proliferation and cell cycle. However, the role of BET proteins on development of regulatory B cells is not reported. In this study, JQ1 potently suppressed IL-10 expression and secretion in murine splenic and peritoneal B cells. While bromodomain-containing protein 4 (BRD4) was associated with $NF-{\kappa}B$ on IL-10 promoter region by LPS stimulation, JQ1 interfered the interaction of BRD4 with $NF-{\kappa}B$ on IL-10 promoter. In summary, BRD4 is essential for toll like receptor 4 (TLR4)-mediated IL-10 expression, suggesting JQ1 could be a potential candidate in regulating IL-10-producing regulatory B cells in cancer.

• The Korean Journal of Pharmacology
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• v.30 no.2
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• pp.205-215
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• 1994

It is well known that chronic stimulation with CCK gives rise to growth of exocrine pancreas and to increased content of enzyme proteins in pancreas. However, littls Is known about changes of the secretory function of exocrine pancreas which has been chronically stimulated with CCK, especially about the responsiveness to secretagogues such as CCK, caerulein and carbachol. The present study was performed to investigate the effect of camostat on secretory profiles and the responsiveness to secretagogues of exocrine pancreas by observing in vitro amylase release stimulated by cholecystokinin-octapeptide(CCK-8) and carbachol in dispersed isolated pancreatic acini from camostat-treated rats for 4 or 10 days. The results summarized as follows : 1) The maximal effective concentration of CCK-8 in amylase release in the camostat treated group was greater than control group, but that of carbachol was not different between groups. 2) Analysis of the stimulated amylase release as the percentage of the maximal response revealed that camostat treatment caused right-shift of the dose-response curve of CCK-8. Camostat did not cause significant changes in the dose-response curve of carbachol. 3) There were considerable increases in the amylase release in the camostat-treated group, compared to the control when acini were stimulated with CCK-8 $10^{-9}\;M$ and carbaochol $10^{-6}\;M$, and higher concentrations. 4) There was a reverse correlation between the tissue content and the maximal release(percent of the total content) of amylase. These results suggest that chronic exposure of exocrine pancreas to increased endogenous CCK can enhance the responsiveness of exocrine enzyme secretion to secretagogues, especially at higher concentrations of CCK and carbachol.

• The Plant Pathology Journal
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• v.36 no.5
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• pp.428-439
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• 2020

Erwinia pyrifoliae is a Gram-negative bacterial plant pathogen that causes black shoot blight in apple and pear. Although earlier studies reported the genome comparison of Erwinia species, E. pyrifoliae strains for such analysis were isolated in 1996. In 2014, the strain E. pyrifoliae EpK1/15 was newly isolated in the apple tree showing black shoot blight in South Korea. This study aimed to better understand the similarities and differences caused by natural variations at the genomic level between newly isolated E. pyrifoliae EpK1/15 and the strain Ep1/96, which were isolated almost 20 years apart. Several comparative genomic analyses were conducted, and Clusters of Orthologous Groups of proteins (COG) database was used to classify functional annotation for each strain. E. pyrifoliae EpK1/15 had similarities with the Ep1/96 strain in stress-related genes, Tn3 transposase of insertion sequences, type III secretion systems, and small RNAs. The most remarkable difference to emerge from this comparison was that although the draft genome of E. pyrifoliae EpK1/15 was almost conserved, Epk1/15 strain had at least three sorts of structural variations in functional annotation according to COG database; chromosome inversion, translocation, and duplication. These results indicate that E. pyrifoliae species has gone natural variations within almost 20 years at the genomic level, and we can trace their similarities and differences with comparative genomic analysis.

• Journal of Microbiology and Biotechnology
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• v.26 no.9
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• pp.1613-1619
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• 2016

Francisella tularensis is a highly virulent pathogen of humans and other mammals. Moreover, F. tularensis has been designated a category A biothreat agent, and there is growing interest in the development of a protective vaccine. In the present study, we determine the in vitro and in vivo immune responses of a subunit vaccine composed of recombinant peptides Tul4 and FopA from epitopes of the F. tularensis outer membrane proteins. The recombinant peptides with adjuvant CpG induced robust immunophenotypic change of dendritic cell (DC) maturation and secretion of inflammatory cytokines (IL-6, IL-12). In addition, the matured DCs enabled ex vivo proliferation of naive splenocytes in a mixed lymphocyte reaction. Lastly, we determined the in vivo immune response by assessment of antibody production in C57BL/6 mice. Total IgG levels were produced after immunization and peaked in 6 weeks, and moreover, Tul4-specific IgG was confirmed in the mice receiving peptides with or without CpG. Based on these results, we concluded that the recombinant peptides Tul4 and FopA have immunogenicity and could be a safe subunit vaccine candidate approach against F. tularensis.

• Microbiology and Biotechnology Letters
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• v.34 no.1
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• pp.1-6
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• 2006

Harmful algal blooms (HABs or red tides), caused by uncontrolled proliferation of marine phytoplankton, impose a severe environmental problem and occasionally threaten even public health. We sequenced the genome of an EPS-producing marine bacterium Hahella chejuensis that produces a red pigment with the lytic activity against red-tide dinoflagellates at parts per billion level. H. chejuensis is the first sequenced species among algicidal bacteria as well as in the order Oceanospirillales. Sequence analysis indicated a distant relationship to the Pseudomonas group. Its 7.2-megabase genome encodes basic metabolic functions and a large number of proteins involved in regulation or transport. One of the prominent features of the H. chejuensis genome is a multitude of genes of functional equivalence or of possible foreign origin. A significant proportion (${\sim}23%$) of the genome appears to be of foreign origin, i.e. genomic islands, which encode genes for biosynthesis of exopolysaccharides, toxins, polyketides or non-ribosomal peptides, iron utilization, motility, type III protein secretion and pigment production. Molecular structure of the algicidal pigment was determined to be prodigiosin by LC-ESI-MS/MS and NMR analyses. The genomics-based research on H. chejuensis opens a new possibility for controlling algal blooms by exploiting biotic interactions in the natural environment and provides a model in marine bioprospecting through genome research.

• Journal of Microbiology and Biotechnology
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• v.23 no.8
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• pp.1116-1122
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• 2013

Cell line development is the most critical and also the most time-consuming step in the production of recombinant therapeutic proteins. In this regard, a variety of vector and cell engineering strategies have been developed for generating high-producing mammalian cells; however, the cell line engineering approach seems to show various results on different recombinant protein producer cells. In order to improve the secretory capacity of a recombinant tissue plasminogen activator (t-PA)-producing Chinese hamster ovary (CHO) cell line, we developed cell line engineering approaches based on the ceramide transfer protein (CERT) and X-box binding protein 1 (XBP1) genes. For this purpose, CERT S132A, a mutant form of CERT that is resistant to phosphorylation, and XBP1s were overexpressed in a recombinant t-PA-producing CHO cell line. Overexpression of CERT S132A increased the specific productivity of t-PA-producing CHO cells up to 35%. In contrast, the heterologous expression of XBP1s did not affect the t-PA expression rate. Our results suggest that CERT-S132A-based secretion engineering could be an effective strategy for enhancing recombinant t-PA production in CHO cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2511-2515
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• 2014

Objective: Lung cancer is one of the malignant tumors with greatest morbidity and mortality around the world. The keys to targeted therapy are discovery of lung cancer biomarkers to facilitate improvement of survival and quality of life for the patients with lung cancer. Translationally controlled tumor protein (TCTP) is one of the most overexpressed proteins in human lung cancer cells by comparison to the normal cells, suggesting that it might be a good biomarker for lung cancer. Materials and Methods: In the present study, the targeted efficacy of dihydroartemisinin (DHA) on TCTP expression in the A549 lung cancer cell model was explored. Results and Conclusions: DHA could inhibit A549 lung cancer cell proliferation, and simultaneously up-regulate the expression of TCTP mRNA, but down-regulate its protein expression in A549 cells. In addition, it promoted TCTP protein secretion. Therefore, TCTP might be used as a potential biomarker and therapeutic target for non-small cell lung cancers.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.6
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• pp.315-322
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• 2005

In this study, the authors investigated whether death of vascular smooth muscle cell (VSMC) had a pathological pertinence. Conditioned media obtained from rat aorta smooth muscle cell (SMC) that were induced death by expressing FADD in the absence of tetracycline (FADD-SMC) triggered death of normal SMC. DNA fragmentation and caspase-3 activation were observed in dying SMC by conditioned media. FADD-SMC showed transcriptional activation of tumor necrosis factor $(TNF)-{\alpha}$. Conditioned medium contained $TNF-{\alpha}$, indicating secretion of the cytokine from dying FADD-SMC. It was investigated if secreted $TNF-{\alpha}$ was functional. Conditioned medium activated ERK and p38 MAPK pathways and induced MMP-9 expression, whereas depletion of the cytokine with its soluble receptor (sTNFR) remarkably inhibited induction of MMP-9 by conditioned medium. These findings suggest that $TNF-{\alpha}$ in conditioned medium seems to be active. Then, contribution of $TNF-{\alpha}$ on death-inducing activity of conditioned medium was examined. Depletion of $TNF-{\alpha}$ with soluble $TNF-{\alpha}$ receptor decreased the death activity of conditioned medium by 35%, suggesting that $TNF-{\alpha}$ play a partial role in the death activity. Boiling of medium almost completely abolished the death-inducing activity, suggesting that other heat labile death inducing proteins existed in conditioned medium. Taken together, these results indicate that SMC undergoing death could contribute to inflammation by expressing inflammatory cytokines and pathological complications by inducing death of neighboring cells.

• Journal of Microbiology and Biotechnology
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• v.17 no.7
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• pp.1162-1168
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• 2007

Although widely used as a host for recombinant protein production, Escherichia coli is unsuitable for massive screening of recombinant clones, owing to its poor secretion of proteins. A vector system containing T4 holin and T7 lysozyme genes under the control of the ptsG promoter derivative that is inducible in the absence of glucose was developed for programmed cell lysis of E. coli. Because E. coli harboring the vector grows well in the presence of glucose, but is lysed upon glucose exhaustion, the activity of the foreign gene expressed in E. coli can be monitored easily without an additional step for cell disruption after the foreign gene is expressed sufficiently with an appropriate concentration of glucose. The effectiveness of the vector was demonstrated by efficient screening of the amylase gene from a Bacillus subtilis genomic library. This vector system is expected to provide a more efficient and economic screening of bioactive products from DNA libraries in large quantities.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3861-3864
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• 2016

Background: Adipokines are bioactive proteins that mediate metabolism, inflammation and angiogenesis. Changes in the secretion of key serum adipokines - adiponectin and letpin - may be associated with obesity, cancer and metabolic disorders. Thyroid cancer is one of the most important types of endocrine cancer. Therefore, investigating the association between serum levels of adiponectin and leptin and thyroid cancer might be important. The purpose of this study was to assess adiponectin and leptin levels in medullary thyroid carcinoma (MTC) cases in order to identify novel tumor markers. Materials and Methods: This research was based on a case-control study, including 45 patients with medullary thyroid cancer (21 men and 24 women) and 45 healthy controls (24 males and 21 females). Adiponectin and leptin levels were measured by ELISA in both groups. Height and weight were measured and body mass index (kg/m2) was calculated. Results: Adiponectin and leptin levels were not significantly different between medullary thyroid carcinomas and the control group. Also, there was no correlation among age and body mass index and the disease. Conclusions: These results suggest that changes in serum adiponectin and leptin levels do not play an important role in the diagnosis or could act as as biomarkers for medullary thyroid cancer.