• 동의신경정신과학회지
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• 제9궈1호
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• pp.73-82
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• 1998

Substantial evidence has accumulated that Alzheimer's disease is associated with a local inflammatory reaction in senile plaques which may be immunemediated, and includes extensive Brain Neuroglial invasion, lymphocytic infiltration, cytokine deposition. Tumor necrosis factor a (TNF-a) is a cytokine which plays an important immunoenhancing role in the local acute and chronic inflammatory response in response to a variety of stimuli. The neuropeptide, substance P, can stimulate secretion of TNF-a from Brain Neuroglial cells. Neuroglia have substance P receptors in the central nervous system. WQ investigated whether RADIX ASPARAGI inhibits secretion of TNF-a from primary cultures of Brain Neuroglial cells containing both astrocyte (∼90%) and microglia (∼10%). RADIX ASPARAGI dose-dependently inhibited the TNF-a secretion induced by substance P plus lipopolysaccharide (LPS). In cultures enriched for micoglia (>95% pure). LPS stimulated the secretion of TNF-a but substance P caused no enhancement. Because there was no synergism between substance P and LPS in the microglial cultures it is resonable to substance P madiated enhancement of TNF-a secretion. IL-1 is a modulator of TNF-a secretion in the immune system. Also IL-1 has been shown to elevate TNF- a secretion from LPS-stimulated Brain Neuroglial cells while having no effect on Brain Neuroglial cells in the absence of LPS. We therfore investigated whether IL-1 mediates the RADIX ASPARAGI inhibition of TNF-a secretion form primary Brain Neuroglial cells. Treatment of RADIX ASPARAGI to mixed cultures stimulated with both substance P and LPS decreased TNF-a secretion to the level observed with LPS alone. These results indicate that RADIX ASPARAGI possess strong antiinflammatory activity in the cental nervous system by inhibition of inflammatory cytokines secretion from Brain Neuroglial cells.

• IMMUNE NETWORK
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• 제4권4호
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• pp.244-249
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• 2004

Background: Corticotropin-Releasing Hormone (CRH), an important regulator of stress response, has a potent immunoregulatory effect with the ability to promote the growth of various cancer through CRH receptor type 1 under stress. Although the metastasized cancers through cell migration are more aggressive than the primary cancers, little is known about the effect of CRH on cell migration. Gastric cancer is prone to metastasize to other tissues and it is reported that gastric cancer is response to various stresses such as oxidative stress. Herein, we studied the relationship between CRH and gastric cancer cell migration. Methods: We used gastric cancer cell line, MKN-28 and tested the CRH receptor type 1 expression on MKN-28 by RT-PCR. To examine the change in the ability of migration by CRH in MKN-28, cells were incubated with CRH and then migration ability was measured using a cell migration assay. Results: We confirmed that CRH receptor type 1 was expressed in MKN-28 and HaCaT cells. The migration ability of MKN-28 cells was increased by CRH in a time-, dose- dependent manner. Conclusion: These data suggest that CRH increases migration ability in gastric cancer cell line and that CRH may be a critical regulator in the metastasis of gastric cancer cell.

• 동의생리병리학회지
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• 제36권1호
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• pp.28-34
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• 2022

Echinacea purpurea (Asteraceae family) is widely used in the European countries and the United States due to its proven immune enhancement and anti-inflammatory effects. Echinacea purpurea has been reported prevent and treat upper respiratory tract infections and common cold, but the underlying molecular mechanisms are not well understood. In the present study, we examined the anti-inflammatory effects and molecular mechanisms of Echinacea purpurea (EP) extract using lipopolysaccharide (LPS)-stimulated signal pathways in RAW264.7 cells. Our results suggest that EP extract exerts anti-inflammatory effects by down-regulating the expression of LPS-induced toll-like receptor 4 (TLR4), subsequently inhibiting the activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathways and suppression of the release of pro-inflammatory cytokines. These results suggest that EP extract is a potential therapeutic agent for inflammatory diseases.

• Clinical and Experimental Pediatrics
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• 제45권3호
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• pp.354-361
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• 2002

목 적: 본 연구에서는 in vitro 및 in vivo에서 HSV-TK 유전자 치료의 bystander 효과 및 기전을 관찰하고, 싸이토카인 유전자의 병합 치료가 bystander 효과를 증폭시킬 수 있는지 조사하여 그 결과를 향후 신경모세포종 치료에 적용하고자 본 연구를 시행하였다. 방 법: A/J 마우스 신경모세포종 모델에서, neuro-2a/TK 세포와 unmodified neuro-2a세포를 여러 비율로 혼합하여 접종한 후 GCV를 투여하여 종양의 크기 변화 및 생존 유무를 관찰하였다. 마우스 신경모 세포종에서 bystander 효과의 기전을 알아보기 위해 neuro-2a/TK 세포를 주입한 마우스의 조직을 절개하여 connexin 43, CD4+ 및 CD8+ 세포 침윤을 관찰 하였다. 10% 및 25% HSV-TK 투여 군에서 neuro-2a/IL-2 세포의 투여가 bystander 효과를 증폭시키는 지 조사하였다. 결 과 : 1) in vitro 및 in vivo에서 bystander 효과는 뚜렷하게 관찰되었다. 2) 마우스 신경모세포종의 면역 조직 화학 염색 검사에서 connexin 43 발현은 관찰되지 않았으나 많은 수의 CD4+ 및 CD8+ T 세포의 침윤이 관찰되었다. 3) 10% 및 25% HSV-TK 투여군의 마우스에서 neuro-2a/IL-2 세포의 투여는 대조군과 비교하여 종양의 성장을 더 억제 시켰다. 결 론: In vitro 및 in vivo에서 HSV-TK/GCV 유전자 치료의 bystander 효과는 뚜렷하였으며, 그 기전으로 면역 세포가 중요한 역할을 할 것으로 추측된다. 그리고 bystander 효과는 IL-2 투여에 의해 증폭됨을 확인하였다. 이는 향후 신경모세포종의 수술 후 잔존암 치료에 HSV-TK/GCV 유전자 치료가 이용 가능할 것으로 생각된다.

• 대한수의학회지
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• 제34권2호
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• pp.287-299
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• 1994

Plasma protein which has been known as one of nonspecific immunostimulators was added to feedstuff to examine its effect on the enhancement of cellular immune response in porcine immune system. A total of 40 piglets, 20 male and 20 female each, were fed for 30 days with or without plasma protein. The peripheral blood were collected and analyzed for the investigation of leukocyte subpopulations and their activities by using a panel of monoclonal antibodies specific to porcine leukocyte differentiation antigens and flow cytometry. The results obtained as follows. 1. Subpopulations expressing major histocompatibility complex(MHC) class I antigen were $96.2{\pm}3.1%$ and $86.6{\pm}3.8%$ in piglets fed with plasma protein and in piglets fed without plasma protein, respectively. 2. Proportion of leukocyte subpopulation expressing MHC class II antigens were significantly higher in the piglets fed with plasma protein than ones without plasma protein. The proportion was $27.6{\pm}3.6%$ and $16.6{\pm}2.2%$ in MHC class II DQ antigen, and $28.1{\pm}2.0%$ and $20.0{\pm}0.3%$ in MHC class II DR antigen, respectively. 3. A significant increase in the proportion of cells expressing poCD2 was not found in piglets fed plasma protein. 4. Proportion of subpopulation expressed porcine(Po) CD4 antigens which specific to helper T lymphocytes were not increased (18.3-19.1% vs. 25.6-28.8%), rather slightly decreased, in plasma protein-treated group. 5. The most important increase of proportion in plasma protein-treated group was the leukocyte subpopulation specific to $poCD8^+$ T cytotoxic/suppressor lymphocytes. The expression level was significantly higher up to 45.9-47.1% in plasma protein-treated group in comparing with 29.7-33.0% in non-plasma protein-treated group. 6. Lymphoblastogenetic responses using different concentrations of Con A mitogen and plasma protein has found that the responses of lymphocyte from piglets fed plasma protein was significantly activated (p<0.01). The activities measured by 3[H]-thymidine incorporation showed 3-6 times stronger in plasma protein-treated group than those in non-plasma protein-treated group. The study has concluded that plasma protein, which has known as a nonspecific immunostimulator, may have an immunoenhancing activities in porcine lymphoid system by increase the activated cell proportions and their blastogenetic properties which is critical to host immune responses.

• IMMUNE NETWORK
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• 제21권5호
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• pp.37.1-37.17
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• 2021

Hepatitis B virus X (HBx) protein has been reported as a key protein regulating the pathogenesis of HBV-induced hepatocellular carcinoma (HCC). Recent evidence has shown that HBx is implicated in the activation of autophagy in hepatic cells. Nevertheless, the precise molecular and cellular mechanism by which HBx induces autophagy is still controversial. Herein, we investigated the molecular and cellular mechanism by which HBx is involved in the TRAF6-BECN1-Bcl-2 signaling for the regulation of autophagy in response to TLR4 stimulation, therefore influencing the HCC progression. HBx interacts with BECN1 (Beclin 1) and inhibits the association of the BECN1-Bcl-2 complex, which is known to prevent the assembly of the pre-autophagosomal structure. Furthermore, HBx enhances the interaction between VPS34 and TRAF6-BECN1 complex, increases the ubiquitination of BECN1, and subsequently enhances autophagy induction in response to LPS stimulation. To verify the functional role of HBx in liver cancer progression, we utilized different HCC cell lines, HepG2, SK-Hep-1, and SNU-761. HBx-expressing HepG2 cells exhibited enhanced cell migration, invasion, and cell mobility in response to LPS stimulation compared to those of control HepG2 cells. These results were consistently observed in HBx-expressed SK-Hep-1 and HBx-expressed SNU-761 cells. Taken together, our findings suggest that HBx positively regulates the induction of autophagy through the inhibition of the BECN1-Bcl-2 complex and enhancement of the TRAF6-BECN1-VPS34 complex, leading to enhance liver cancer migration and invasion.

• 대한한방부인과학회지
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• 제18권3호
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• pp.51-66
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• 2005

Purpose : Investigate the effects of Haeganjeon water extract (HGJ) on immobilization-stress or cold-stress in C57BL/6J mice. Methods : Male C57BL/6J 30 mice of weighting 18${\pm}$2g, were divided into sixs groups including the immobilization-stress group(5heads), after immobilization-stress HGJ oral administration(500mg/kg) groups(5heads), cold-stress group(5heads) and after cold-stress HGJ oral administration(500mg/kg) groups(5heads). then we observed changes in the serum histamine and corticosterone level and changes immune system. Results : HGJ decreased the serum level of histamine and corticosterone increased by immobilization-stress or cold-stress. HGJ inhibited the release of histamine from mast cells. In addition, HGJ enhanced the cell viability of thymocytes decreased by immobilization-stress or cold-stress and decreased DNA fragmentation of thymocytes increased by immobilization- stress or cold-stress. Also, HGJ increased the cell viability of splenocytes decreased by cold-stress and decreased DNA fragmentation of splenocytes increased by cold-stress. HGJ decreased the population of thymic CD4+ cells increased by immobolization-stress. HGJ increased the population of B220+ cells decreased by immobilization-stress and decreased the population of Thy1+ cells increased by immobilization-stress. Also, HGJ decreased the population of splenic CD4+ cells increased by immobolization-stress. HGJ enhanced the production of ${\gamma}-interferon$ decreased by immobilization-stress or cold-stress and increased the production of interleukin-4 decreased by immobilization-stress. Furthermore, HGJ enhanced the phagocytic activity decreased by immobilization-stress or cold-stress and enhanced the level of nitric oxide decreased by immobilization-stress or cold-stress. Conclusion : HGJ may be useful for the prevention and treatment of stress via suppression of serum histamine and corticosterone level and enhancement of immune response.

• 대한한의학방제학회지
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• 제5권1호
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• pp.147-168
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• 1997

Tish study was carried out to evaluate the possible therapeutic or antitumoral effects of Takrisodokyeum extract against tumor, and immunomodulatory effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene (MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S-I80 and Fas II cells). Treatment of the Takrisodokyeum water-extract(daily 1mg mouse, i.p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 15 days. Against squamous cell carcinoma induced by MCA, Takrisodokyeum decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice (TBM). Takrisodokyeum also significantly suppressed the development of 3LLcell and S-180 cell by frequency and their size, and some developed tumors were regressed by the continuous treatment of Takrisodokyeum extract into TBM. However, when tumor was induced by FsaII cell-implantation, the growth of implanted cells in mice was delayed by the water extract of Takrisodokyeum until day 7 and then rapid growth ensued. In vitro, treatment of Takrisodokyeum extract had no effect on the growth of some kind of cell lines such as FsaII, A-131 strain but significantly inhibited the proliferation of 3LL, S-180 cells. Takrisodokyeum also stimulated the migrative ability of leucocyte, the MIF and IL 2-production of T lymphocytes, but not IL 6 production of B cells. Takrisodokyeum enhanced Arthus reaction and DTH to sheep erythrocytes, and NK cells activities. These results demonstrated that Takrisodokyeum extract different results according to the type of tumor cells. And these results also suggested that antitumor effect of Takrisodokyeum might be chiefly due to nonspecific enhancement of NK cell activities and cell-mediated immune responses.

• Animal Bioscience
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• 제35권5호
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• pp.721-729
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• 2022

Objective: An experiment was conducted to determine the effects of supplementing graded concentrations of inorganic sulphur (S) without and with folic acid (FA) in maize-soybean meal diets on performance, slaughter and anti-oxidant variables, immune responses and serum protein fractions in broiler chicken. Methods: Inorganic S was supplemented at 0.05%, 0.10%, 0.15%, and 0.20% alone or in combination with FA (4 mg/kg) in basal diet (BD) containing no supplemental methionine (Met) and FA. A control group was fed with the recommended concentration of Met. Each diet was offered to 10 pens of 5 male broiler chicks (Cobb 400) and fed ad libitum from day 1 to 42. Results: The broilers fed the BD had lower body weight gain (BWG), feed efficiency (FE), higher lipid peroxidation (LP), lower activity of glutathione peroxidase (GSHPx), lower lymphocyte proliferation ratio (LPR), and reduced concentrations of total protein, albumin, and globulin in serum. Supplementation of FA and S to the BD improved the BWG (all concentrations of S) and FE (0.20% S) similar to the control group. Similarly, the combination of S and FA significantly improved the concentrations of total protein, albumin, and globulin in serum, reduced the LP and increased the activity of GSHPx and LPR. However, responses in the above parameters were related to the concentration of S in the diet. The slaughter variables and antibody titres against the Newcastle disease were not affected with the treatments. Conclusion: Based on the results, it is concluded that the combination of S (0.2%) and FA (4 mg/kg) improved the BWG and FE, similarly supplementation of these nutrients improved the concentration of protein fractions and reduced the stress (reduced LP and improved GSHPx) variables in serum and improved the cell mediated immune response (LPR) in broilers fed sub-optimal concentrations of Met in diet.

• Journal of Microbiology and Biotechnology
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• 제34권6호
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• pp.1299-1306
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• 2024

Antibiotics are used to control infectious diseases. However, adverse effects of antibiotics, such as devastation of the gut microbiota and enhancement of the inflammatory response, have been reported. Health benefits of fermented milk are established and can be enhanced by the addition of probiotic strains. In this study, we evaluated effects of fermented milk containing Lacticaseibacillus rhamnosus (L. rhamnosus) SNUG50430 in a mouse model with antibiotic treatment. Fermented milk containing 2 × 10⁵ colony-forming units of L. rhamnosus SNUG50430 was administered to six week-old female BALB/c mice for 1 week. Interleukin (IL)-10 levels in colon samples were significantly increased (P < 0.05) compared to water-treated mice, whereas interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were decreased, of mice treated with fermented milk containing L. rhamnosus SNUG50430-antibiotics-treated (FM+LR+Abx-treated) mice. Phylum Firmicutes composition in the gut was restored and the relative abundances of several bacteria, including the genera Coprococcus and Lactobacillus, were increased in FM+LR+Abx-treated mice compared to PBS+Abx-treated mice. Interestingly, abundances of genus Coprococcus and Lactobacillus were positively correlated with IL-5 and IL-10 levels (P < 0.05) in colon samples and negative correlated with IFN-γ and TNF-α levels in serum samples (P < 0.001). Acetate and butyrate were increased in mice with fermented milk and fecal microbiota of FM+LR+Abx-treated mice were highly enriched with butyrate metabolism pathway compared to water-treated mice (P < 0.05). Thus, fermented milk containing L. rhamnosus SNUG50430 was shown to ameliorate adverse health effects caused by antibiotics through modulating immune responses and the gut microbiota.