• 한국발생생물학회지:발생과생식
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• 제21권1호
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• pp.35-46
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• 2017

The process of spontaneous abortion involves a complex mechanism with various cytokines, growth factors, and hormones during the pregnancy. However, the mechanism underlying spontaneous abortion by pro- and anti-inflammatory cytokines in the serum during the pregnancy is not fully understood. Therefore, the purpose of this study was to examine the relationship between the serum levels of pro- and anti-inflammatory cytokines and spontaneous abortion using the $CBA/j{\times}DBA/2$ mouse model. Serum levels of pro-inflammatory cytokines, such as $IFN-{\gamma}$, $IL-1{\alpha}$ and $TNF-{\alpha}$ were not increased in abortion model mice, but anti-inflammatory cytokines, such as IL-4, IL-13 and IL-1ra were decreased compared to normal pregnant mice. In addition, serum levels of chemokine, such as SDF-1, G-CSF, M-CSF, IL-16, KC and MCP-1 were decreased in abortion model mice compared to normal pregnant mice. However, the expression levels of nesfatin-1/NUCB2 mRNA and protein in the uteri of implantation sites were significantly higher in abortion model mice than normal pregnant mice. These results suggest that uterine nesfatin-1/NUCB2 expression may be down-regulated by inflammatory cytokines and chemokines in the serum of pregnant mice. Moreover, this study suggests the possibility that nesfatin-1/NUCB2 expressed in the implantation sites may be associated with the maintenance of pregnancy.

• Biomolecules & Therapeutics
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• 제12권1호
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• pp.25-33
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• 2004

In this study we investigated whether ATP loss was involved in the potentiated death of immunostimulated rat primary astrocytes in glucose-deprived condition. Rat primary astrocytes immunostimulated with LPS plus IFN-${\gamma}$ for 48 h underwent death upon glucose deprivation, which dependent on the production of peroxynitrite. Intracellular ATP level synergistically decreased by glucose deprivation in immunostimulated astrocytes but not in control cells, and the loss of ATP occurred well ahead of the LDH release. The synergistic cell death and ATP loss by immunostimulation and glucose deprivation were inhibited by iNOS inhibitor (L-NAME and L-NNA) or peroxynitrite decomposition catalyst (also a superoxide anion scavenger), Mn(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (MnTMPyP). Exogenous addition of peroxynitrite generator, SIN-l timedependently induced ATP loss and cell death in the glucose-deprived astrocytes. Depletion of intracellular glutathione (GSH) and dis겨ption of mitochondrial transmembrane potential (MTP) were also observed under same conditions. Supply cellular ATP by the addition of exogenous adenosine or ATP during glucose deprivation inhibited ATP depletion, GSH depletion, MTP disruption and cell death in SIN-l treated or immunostimulated astrocytes. This study showed that perturbation in the regulation of intracellular ATP level in immunostimulated astrocytes might make them more vulnerable to energy challenging stimuli.

• Parasites, Hosts and Diseases
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• 제55권5호
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• pp.505-512
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• 2017

Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or absence of the adjuvant ${\alpha}-GalCer$. As results, TgCPC1 DNA vaccine with or without adjuvant ${\alpha}-GalCer$ showed higher levels of IgG and IgG2a in the serum, as well as IL-2 and $IFN-{\gamma}$ in the spleen compared to controls (PBS, pEGFP-C1, and ${\alpha}-GalCer$). Upon challenge infection with tachyzoites of T. gondii (RH), $pCPC1/{\alpha}-GalCer$ immunized mice showed the longest survival among all the groups. Mice vaccinated with DNA vaccine without adjuvant (pCPC1) showed better protective immunity compared to other controls (PBS, pEGFP-C1, and ${\alpha}-GalCer$). These results indicate that a DNA vaccine encoding TgCPC1 is a potential vaccine candidate against toxoplasmosis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5747-5751
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• 2013

Golgi phosphoprotein 2 (GOLPH2) is a very important biomarker in a variety of diseases. Its biological function is not clear, particularly in gastric cancer. To investigate the role of GOLPH2 in human gastric cancer, and determine its effect on the Th1 lymphocyte response, its expression and that of IL-12A were measured by real-time PCR and immunohistochemistry. The relationship between GOLPH2 and IL-12A was analysed statistically. The effect of GOLPH2 on the Th1 lymphocyte response was investigated with an in vitro co-culture system. The results showed that in human gastric cancer, the expression of GOLPH2 was significantly higher and the expression of IL-12A was lower than in normal gastric mucosal tissues, and the expression levels of GOLPH2 and IL-12A were negatively correlated. In addition, obvious down-regulation of the Th1 response was observed when lymphocytes were co-cultured with gastric cancer SGC7901 cells over-expressing GOLPH2. GOLPH2 down-regulated the expression of IL-12A, and inhibited the expression of TNF-${\alpha}$ and IFN-${\gamma}$. The results indicated that GOLPH2 down-regulates the Th1 response via suppression of IL-12A in human gastric cancer, and this might provide a target for the prevention and treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3551-3558
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• 2016

Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world, with chronic inflammation and diet as major causes in its development. Chemopreventive effects of natural dietary products have been the focus of studies for prevention over the past decade. This study was conducted to determine the effects of unpolished Thai rice during precancerous stage through the involvement of ${\beta}$-catenin, cyclooxygenase-2 (COX-2) expression and inflammatory cytokines focusing on azoxymethane (AOM)-induced aberrant crypt foci (ACF)-related to CRC. Male Sprague Dawley rats received two injections of AOM (15 mg/kg body weight) at weeks 4 and 5 while rats were treated with 20% or 70% unpolished Thai rice. The rats were sacrificed at week 38 and the colons removed for aberrant crypt foci (ACF) identification. Histopathologic changes, immunohistochemical analysis of ${\beta}$-catenin and COX-2 expression, and cytokine expression of proinflammatory and anti-inflammatory markers were determined. The administration of unpolished Thai rice significantly and dose dependently decreased the total number of ACF and the percentages of ACF with high-grade dysplasia. Interestingly, unpolished Thai rice suppressed the expression of ${\beta}$-catenin and COX-2. In addition, it also altered proinflammatory (IL-6 and IFN-${\gamma}$) and anti-inflammatory (IL- 10) markers. The results suggested that unpolished Thai rice may provide a promising dietary intake for prevention during precancerous stage of CRC development, through the involvement of ${\beta}$-catenin and COX-2 expression, and also modulate inflammatory cytokines-related to CRC.

• IMMUNE NETWORK
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• 제15권3호
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• pp.150-160
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• 2015

We previously reported that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) accelerates hematopoiesis and has an improving effect on animal disease models such as sepsis and asthma. The effects of PLAG supplementation on immune modulation were assessed in healthy men and women. The objective was to evaluate the effects of PLAG supplementation on immune regulatory functions such as activities of immune cells and cytokine production. A randomized double blind placebo-controlled trial was conducted. Seventy-five participants were assigned to one of two groups; all participants had an appropriate number of white blood cells on the testing day. The PLAG group (n=27) received oral PLAG supplements and the control group (n=22) received oral soybean oil supplements. IL-4 and IL-6 production by peripheral blood mononuclear cells (PBMC) were lower (p<0.001 and p<0.001, respectively) with PLAG than with soybean oil. However, the production of IL-2 and IFN-$\gamma$ by PBMC was unaltered with PLAG supplementation. The B cell proliferation decreased significantly in the PLAG group compared to the soybean oil control (p<0.05). The intake of PLAG in healthy adults for 4 weeks was deemed safe. These data suggest that PLAG has an immunomodulatory function that inhibits the excessive immune activity of immunological disorders such as atopic and autoimmune diseases. PLAG could improve the condition of these diseases safely as a health food supplement.

• 대한본초학회지
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• 제30권3호
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• pp.1-12
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• 2015

Objectives : In this study, we investigated the effects of Agastachis Herba water (AH-W) extract on compound 48/80-induced mast cell degranulation and histamine release in human mast cells and also anti-asthmatic effect of AH-W extract on ovalbumin (OVA)-induced asthma in mice. Methods : Human mast cells, HMC-1 were treated with AH-W extract in the presence or absence of compound 48/80 (C48/80). Mast cell degranulation was observed by microscope, and the histamine release was measured in culture medium by ELISA. For preparation of asthmatic in vivo model, mice were sensitized (0, 7, and 14 days) with OVA and airway challenged (21, 23, 25, 27, and 29 days). AH-W extract at doses of 100 and 300 mg/kg/body weight was orally administered during OVA challenge once per a day. The levels of immunoglobulin (Ig) E, and Th1/Th2 cytokines, IFN-$\gamma$ and IL-4 were measured in the sera of mice by ELISA. The histopathological change of lung tissues was observed by hematoxylin and eosin (H&E) and Periodic Acid Schiff (PAS) staining. Results : The treatment of AH-W extract significantly decreased the mast cell degranulation and histamine release in C48/80-stimulated HMC-1 cells. In addition, The administration of AH-W extract at does of 100 and 300 mg/kg significantly decreased the serum levels of OVA-specific IgE compared with those of OVA control group. In H&E and PAS staining, AH-W extract inhibited OVA-induced airway inflammation, and inflammatory cells infiltration, and also histopathological damages on lung tissues such as bronchiole epithelial desquamation, goblet cells hyperplasia, and mucin releasing. Conclusions : These results indicate that AH-W extract may improve asthmatic symptoms through mast cell stabilization and inhibiting the lung inflammation in bronchial asthma.

• 한국약용작물학회지
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• 제19권1호
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• pp.16-23
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• 2011

This study was conducted to investigate the anti-inflammatory effects of Pruns mume, Schisandra chinensis, Chaenomeles sinensis-- Prunus mume mixtrue (PM) treatment on colitis induced in mice by dextran sodium sulfate (DSS) treatment. A total of 25 male BALB/c mice (average weight $20.7\;{\pm}\; 1.6 \;g$) were divided into 5 treatment groups and fed a commercial diet (A), PM administration (B), commercial diet + induced colitis by DSS (C), PM administration + induced colitis by DSS (D) and sulfasalazine + induced colitis by DSS (E). We found that PM treatment (D) and sulfasalazine (E) decreased the expression of $TNF-{\alpha}$ and COX-2 compared to the DSS-induced colitis group (C). The expression of IL-4, STAT6, $IFN-{\gamma}$, STAT1 was decreased in group D and group E compared to the colitis group (C), COX-2 and STAT1 were more decreased in group D. The serum IgE levels decreased in the PM treatment groups (C and D) compared to the non-PM treatment groups (A and B) although there was no significant difference between the PM treatment groups. It is notable that a therapeutic application of the PM extracts ameliorated DSS-induced colitis in mice.

• 대한한의학회지
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• 제34권4호
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• pp.1-11
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• 2013

Objectives: Galgeun-tang (GGT, gegen-tang, kakkon-to), an herbal formula, is used to treat the common cold, fevers, headaches, hangovers and neck and upper back stiffness. The drugs currently used to treat atopic dermatitis (AD) are limited by the significant adverse effects associated with their long-term usage. The need to efficiently manage the AD response while reducing side effects has led to the development of alternative remedies. Methods: To assess the effects of GGT on AD, the anti-inflammatory and anti-AD properties of GGT were evaluated in both in vitro and in vivo systems. Results: Nitric oxide (NO) and histamine production on lipopolysaccharide (LPS)-treated RAW264.7 cells and phorbol-12 myristate 13-acetate (PMA)/A23187-treated MC/9 cells, respectively, were inhibited by GGT. GGT reduced thymus and activation-regulated chemokine (TARC/CCL17) release on TNF-${\alpha}$/IFN-${\gamma}$ stimulated HaCaT cells in a dose-dependent manner. GGT reduced both plasma levels of IgE and histamine and the dermatitis score in house dust mite induced atopic dermatitis-like lesions on NC/Nga mice. However, there were no significant histopathological differences observed between the GGT group and the AD-induced group, such as AD-like lesions in the dorsal skin or ear or mast cell infiltration in the dorsal skin. Conclusions: These results indicate that GGT inhibits chemokine production by keratinocytes and the atopic dermatitis response in NC/Nga mice, suggesting that GGT may be useful as a therapeutic remedy for treating AD and allergic inflammation-related diseases.

• 대한한방소아과학회지
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• 제30권2호
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• pp.96-106
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• 2016

Objectives The purpose of this study is to investigate the effects of Gleditsiae Fructus 70% EtOH extract (JS_E) on anti-inflammatory action in HaCaT cells (A spontaneously immortalized human keratinocyte cell line) and inhibiting triglyceride genesis in SEB-1 cells (Immortalized human sebocyte). Methods The anti-inflammatory effect of JS_E was analyzed by enzyme-linked immunosorbent assays (ELISA) which measured levels of IP-10, RANTES and MDC in HaCaT cells. Also the effect on secretion of sebum of JS_E was analyzed by TG-S kit which measured the quantity of triglyceride in SEB-1 cells. Results JS_E inhibited IP-10, RANTES and MDC expression in a dose dependent manner. IP-10 expression was inhibited significantly in comparison to TNF-${\alpha}$ and IFN-${\gamma}$ recombination (TI) control group at concentration of JS_E $200{\mu}g/ml$ and RANTES and MDC expressions were inhibited significantly at concentration of JS_E 100, $200{\mu}g/ml$. JS_E also inhibited triglyceride secretion of SEB-1 cells significantly in comparison to the control group in a dose dependent manner. Conclusions This study shows that JS_E has the effects of anti-inflammatory action and inhibiting sebum secretion. According to these results, JS_E can be used for treating skin diseases such as acne and dermatitis caused by inflammation and excessive secretion of sebum by controlling the activity of the HaCaT and SEB-1 cells.