• Parasites, Hosts and Diseases
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• 제29권3호
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• pp.279-292
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• 1991

마우스에의 돼지회충(Ascaris strum) 또는 선모충(Trichinella spiralis) 감염이 sRBC에 대한 면역능에 미치는 영향을 조사한 다음 전처치로서 선모충을 감염시키거나 또는 cyclophosphamide를 투여하고 나서 돼지회충란을 경구투여하여 그 감염상태와 소장점막내 비만세포와의 관련성 그 리고 비특이 세포성 및 체액성 면역능을 함께 관찰하였다. 마우스에 1,000개의 돼지회충란을 경구투여한 바 지연형 과민반응과 로제트 형성능은 시일이 경과됨에 따라 점점 감소하기 시작하여 각각 5주, 6주에 최저치에 이른 다음 점점 상승하여 10주에 원상으로 복귀하였으며, 적현구 응집소가 및 용현소가는 점점 상승하여 3주에 최고치에 이른 다음 그 후 정상으로 복귀하였으며, 말초힐액내 호산구 및 소장접막내 비만세포 출현율은 각각 4주 및 2주에 최고치를 보였다. 한편, 유충은 1주후에 폐와 간으로부터 총 21.97%가 누수되었다. 마우스에 300마리의 선모충의 감염유충을 경구투여한 바 지연형 과민반응과 로제트 형성능은 시일이 경과 됨에 따라 점점 낮아져 각각 30일 및 21일에 전저치에 이른 다음 그 후부터 다소 높아지다가 70일 및 80일에 다시 일시적으로 낮아졌다. 그리고, 적현구 응집소가 및 용혈소가도 각각 21일 및 90일 에 다른 기보다 낮았으나, 말초혈액내 호산구 및 소장점막내 비만세포 출현율은 각각 40일째 및 14 일째에 다른 기보다 높았다. Cyclophosphamide를 400 mg/kg의 용량으로 마우스의 복륙 내에 투여한 바 체중이나 비장의 중량, 지연형 과민반응, 로제트 형성능, 적혈구 응집소가 및 용혈소가, 백현구 총수, 소장점막내 비만세포 출현율은 투여 후 1일에 비하여 5일에 현저하게 저하되었다가 10일에 다 시 증가하여 1일과 거의 비슷한 수준으로 복귀하였다. 말포혈액내 호산구 출현율은 시일이 경과함 에 따라 점점 낮아지는 경향이었다. 한편, 마우스의 복강 내에 cyclophosphamide를 투여한 다음 1일, 5일, 10일에 각각 1,000개의 감염성 돼지회충란을 투여하고 난 후 7일의 유충각수률은 1일 7.07%, 5일 14.94%, 10일 10.1%이었으며 대조군은 8.02%이었다 유모충을 마우스에 감작감염시키고 나서 각각 30일 및 70일 간격을 두고 감염성 돼지회충란을 도전감염시킨 바 참작감염후 37일과 도전감염후 7일의 시점에 있어서 지연형 과민반응과 로제트 형성능은 고도로 저하하였는데 반하여 소장점막내 비만세포 출현율은 고도로, 말초혈액내 호산구출현율, 적혈구 응집소가 및 용혈소가는 상당히 증가하였다. 이 시점에 있어서의 유충은 대조가 22.18% 회수되었는데 비하여 9.3%밖에 회수되지 않았다. 한편, 감작감염후 77일과 도전감염후 7일의 시점에 있어서 sRBC에 대한 면역능에 미치는 영향은 전자의 양상과 비슷하였는데 대조에 비하여 지연형 과민반응과 로제트 형성능이 현저하게 저하되었다. 이 시점에 있어서의 유충회수율은 대조가 10.5% 이었는데 비하여 8.3%이었다.

• 대한의생명과학회지
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• 제19권2호
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• pp.118-123
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• 2013

Tumor necrosis factor-alpha (TNF-${\alpha}$) is a proinflammatory cytokine that mediates the inflammatory response and immune functions, and modulates the proliferation, differentiation and cell death of cancer cells. The differential functions of TNF-${\alpha}$ in various human cells due to the formation of different stimulating pathway upon the binding of TNF-${\alpha}$ to its receptors. In the present study, we examined the different effects of TNF-${\alpha}$ on the survival and apoptosis between normal granulocytes and human myeloid leukemia HL-60 cells. Although TNF-${\alpha}$ did not affect on the constitutive apoptosis of granulocytes, TNF-${\alpha}$ strongly induced the apoptosis of HL-60 cells in a dose- and a time-dependent manner. TNF-${\alpha}$-induced apoptosis was occurred via the activation of caspase 8, caspase 9 and caspase 3/7 and the induction of ROS production in HL-60 cells. Also, BAY-11-7085, a NF-${\kappa}B$ inhibitor, blocked the TNF-${\alpha}$-induced apoptosis in HL-60 cells. NF-${\kappa}B$ may be involved in TNF-${\alpha}$-induced apoptotic signaling pathway in HL-60 cells. These results suggest that TNF-${\alpha}$ activates apoptotic pathways and its process depends on cell type and many cellular factors. A better understanding of the differential effect of TNF-${\alpha}$ on cell apoptosis and survival may provide important information that can be used to elucidate the specific inhibitory effect of TNF-${\alpha}$ on the cancer dis.

• IMMUNE NETWORK
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• 제2권3호
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• pp.133-136
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• 2002

Background: The costimulatory molecule 4-1BB, a member of nerve growth factor receptor/tumor necrosis factor (NGFR/TNFR) super family, is involved in cell survival and death. Methods: In this study, female C57BL/6 ($H-2^b$) mice were used as a recipient, and DBA/2 ($H-2^d$) as a donor to assess a mixed lymphocyte reaction (MLR) and CTL response in vitro, and skin graft survival. IL-2, IFN level was measured by ELISA. Results: Mixed lymphocyte reaction (MLR) analysis showed that 4-1BB-deficient responder cells showed enhanced cellular proliferation over littermate controls. In contrast, IL-2 production was diminished only in 4-1BB knockout cultures. The IFN expression, on the other hand, was comparable between the groups. When female C57BL/6 ($H-2^b$) mice were grafted with the trunk skin of DBA/2 ($H-2^d$) mice, the in vivo tissue destruction of 4-1BB-deficient mice was not distinct from the normal littermates. Conclusion: These data suggest that 4-1BB is critical for the induction of alloreactive responses in vitro but 4-1BB alone could not change the course of skin rejection in vivo.

• Journal of Microbiology and Biotechnology
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• 제28권1호
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• pp.136-144
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• 2018

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Bacillus Calmette-$Gu\acute{e}rin$ (BCG) vaccine is the only TB vaccine currently available, but it is not sufficiently effective in preventing active pulmonary TB or adult infection. With the purpose of developing an improved vaccine against TB that can overcome the limitations of the current BCG vaccine, we investigated whether adjuvant formulations containing de-O-acylated lipooligosaccharide (dLOS) are capable of enhancing the immunogenicity and protective efficacy of TB subunit vaccines. The results revealed that the dLOS/dimethyl dioctadecyl ammonium bromide (DDA) adjuvant formulation significantly increased both humoral and Th1-type cellular responses to TB subunit vaccine that are composed of three antigens, Ag85A, ESAT-6, and HspX. The adjuvanted TB vaccine also effectively induced the Th1-type response in a BCG-primed mouse model, suggesting a potential as a booster vaccine. Finally, the dLOS/DDA-adjuvanted TB vaccine showed protective efficacy against M. tuberculosis infection in vitro and in vivo. These data indicate that the dLOS/DDA adjuvant enhances the Th1-type immunity and protective efficacy of the TB subunit vaccine, suggesting that it would be a promising adjuvant candidate for the development of a booster vaccine.

• IMMUNE NETWORK
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• 제13권5호
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• pp.213-217
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• 2013

Enterotoxigenic Bacteroides fragilis (ETBF) is a human gut commensal bacteria that causes inflammatory diarrhea and colitis. ETBF also promotes colorectal tumorigenesis in the Min mouse model. The key virulence factor is a secreted metalloprotease called B. fragilis toxin (BFT). BFT induces E-cadherin cleavage, cell rounding, activation of the ${\beta}$-catenin pathway and secretion of IL-8 in colonic epithelial cells. However, the precise mechanism by which these processes occur and how these processes are interrelated is still unclear. E-cadherin form homophilic interactions which tethers adjacent cells. Loss of E-cadherin results in detachment of adjacent cells. Prior studies have suggested that BFT induces IL-8 expression by inducing E-cadherin cleavage; cells that do not express E-cadherin do not secrete IL-8 in response to BFT. In the current study, we found that HT29/C1cells treated with dilute trypsin solution induced E-cadherin degradation and IL-8 secretion, consistent with the hypothesis that E-cadherin cleavage causes IL-8 secretion. However, physical damage to the cell monolayer did not induce IL-8 secretion. We also show that EDTA-mediated disruption of E-cadherin interactions without E-cadherin degradation was sufficient to induce IL-8 secretion. Finally, we determined that HT29/C1 cells treated with LiCl (${\beta}$-catenin activator) induced IL-8 secretion in a dose-dependent and time-dependent manner. Taken together, our results suggest that BFT induced IL-8 secretion may occur by the following process: E-cadherin cleavage, disruption of cellular interactions, activation of the ${\beta}$-catenin pathway and IL-8 expression. However, we further propose that E-cadherin cleavage per se may not be required for BFT induced IL-8 secretion.

• Journal of Periodontal and Implant Science
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• 제30권3호
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• pp.675-687
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• 2000

Multiple periodontal pathogens sequentially colonize the subgingival niche during the conversion from gingivitis to destructive periodontal disease. An animal model of sequential immunization with key periodontal pathogens has been developed to determine whether T and B lymppocyte effector functions are skewed and fail to protect the host from pathogenic challenge. The present study was performed to evaluate immunomodulatory effect of exposure to Fusobacterium nucleatum(F. nucleatum) prior to Porphyromonas gingivalis(P. gingi - valis). Group 1(control) mice were immunized with phosphate-buffered saline, Group 2 were immunized with F. nucleatum prior to P. gingivalis, while Group 3 were immunized P. gingivalis alone. All the T cell clones derived from Group 2 demonstrated type 2 helper T cell clone(Th2 subsets), while those from Group 3 mice demonstrated Th1 subsets. Exposure of mice to F . nucleatum prior to P. gingivalis interfered with opsonophagocytosis function of sera against P. gingivalis. In adoptive T cell transfer experiments, in vivo protective capacity type 2 helper T cell clones(Th2) from Group 2 was significantly lower than type 1 helper T cell clones(Th1) from Group 3 against the lethal dose infection of P. gingivalis. Western blot analysis indicated the different pattern of recognition of P .gingivalis fimbrial proteins between sera from Group 2 and Group 3. In conclusion, these study suggest that colonization of the subgingival niche by F .nucleatum prior to the periodontal pathogen, P. gingivalis, modulates the host immune responses to P. gingivalis at humoral, cellular and molecular levels.

• 동의신경정신과학회지
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• 제19권3호
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• pp.55-68
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• 2008

Background: Microglia produces a barrage of factors (IL-l, TNF-$\alpha$, NO, superoxide) that are toxic to neurons and playa major role in the cellular immune response associated with the pathology of Alzheimer's disease(AD). OJaJiHwangEumJa(OJJHEJ) has been usually used for the treatment of senile disorders. For enhancing efficacy and convenience, the change of the drug delivery device of oriental herbal medicine is required. Objective: This experiment was designed to investigate the effect of the OJJHEJ hot water extract & ultra-fine powder on proinflammatory cytokine of microglia and memory deficit model. Method: The effects of the OJJHEJ hot water extract on production of IL-1$\beta$, IL-6, TNF-$\alpha$, in BV2 microglial cell line treated by lipopolysacchaide(LPS) were investigated. The effects of the OJJHEJ hot water extract & ultra-fine powder on the behavior of the memory deficit mice induced by scopolamine and AChE in serum of the memory deficit mice induced by scopolamine were investigated. Results: 1. The OJJHEJ hot water extract suppressed the production of IL-1$\beta$, IL-6, TNF-$\alpha$ in BV2 microglial cell line and the production of IL-6 was suppressed significantly. 2. The OJJHEJ hot water extract & ultra-fine powder decreased AChE significantly in the serum of the memory deficit mice induced by scopolamine. 3. The OJJHEJ hot water extract & ultra-fine powder groups showed significantly inhibitory effect on the scopolamine-induced impairment of memory in the experiment of Morris water maze. Conclusions: This experiment shows that the OJJHEJ hot water extract & ultra-fine powder might be effective for the prevention and treatment of memory impairment diseases. Investigation into the clinical use of the OJJHEJ hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4217-4224
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• 2014

Cholangiocarcinoma (CCA), a slow growing but highly metastatic tumor, is highly prevalent in Northeast Thailand. Specific tests that predict prognosis of CCA remain elusive. The present study was designed to investigate whether peripheral blood leukocyte (PBL) transcriptional profiles might be of use as a prognostic test in CCA patients. Gene expression profiles of PBLs from 9 CCA and 8 healthy subjects were conducted using the Affymetrix HG_U133 Plus 2.0 GeneChip. We indentified informative PBLs gene expression profiles that could reliably distinguish CCA patients from healthy subjects. Of these CCA specific genes, 117 genes were up regulated and 60 were down regulated. The molecular and cellular functions predicted for these CCA specific genes according to the Gene Ontology database indicated differential PBL expression of host immune response and tumor progression genes (EREG, TGF ${\beta}1$, CXCL2, CXCL3, IL-8, and VEGFA). The expression levels of 9 differentially expressed genes were verified in 36 CCA vs 20 healthy subjects. A set of three tumor invasion related genes (PLAU, CTSL and SERPINB2) computed as "prognostic index" was found to be an independent and statistically significant predictor for CCA patient survival. The present study shows that CCA PBLs may serve as disease predictive clinically accessible surrogates for indentifying expressed genes reflective of CCA disease severity.

• Journal of Acupuncture Research
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• 제23권6호
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• pp.103-115
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• 2006

Objectives : Rheumatoid arthritis(RA) is a systemic & a chronic inflammatory autoimmune disease . A chronic , locally destructive inflammmatory reaction in human is examplified by the synovitis present in some connective tissue disorder. The presence of a number of cytokines, $TNF-{\alpha}$, iNOS & expression of nitric oxide, NF-kB p65 activation implies an important role of cellular immune response in RA inflammatory reaction. This study was designed to evaluate on the effects of the Homnis Placenta herbal acupuncture on EX-LE201 & ST 35 reducing expression of LPS-induced arthritis model in mice. Materials and Methods : Homnis Placenta herbal acupuncture was inserted into 10 rats induced rheumatoid arthritis. The acupunctures were injected into the EX-LE201 and ST35 points. Such indexes were measured the inhibition of inducible nitric oxide synthase(iNOS) expression, nitric oxide(NO) production in vitro experiment and Tumor Necrosis $Factor-{\alpha}(TNF-{\alpha})$ & Nuclear Factor kappa $B(NF-{\kappa}B)$ p65 activation, synovial hyperplasia, angiogenesis and fibrosis in synovial membrane of knee joint of mice in vivo experiment. Results : 1.Homnis Placenta Herbal acupuncture inhibited iNOS mRNA and NO in RAW 264.7 cell of LPS-induced rheumatoid arthritis in a dose dependent manner. 2.Homnis Placenta Herbal acupuncture also showed significant inhibition of $TNF-{\alpha}$ & $NF-{\kappa}B$ p65, activation, synovial hyperplasia, angiogenesis and fibrosis in synovial membrane of knee joint of mice. Conclusion : These results suggest that Homnis Placenta Herbal acupuncture has an therapeutic effects on LPS induced-rheumatoid arthritis by inhibiting $TNF-{\alpha}$ activation.

• International Journal of Oral Biology
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• 제30권1호
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• pp.1-8
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• 2005

The elderly suffer from an impaired immune function being obvious in a higher susceptibility to infections. Although the inflammatory cells are the major immunomodulatory cells, fibroblasts also secrete a variety of inflammatory cytokines and chemokines. Therefore periodontal tissue aging might playa role in development and progress of periodontitis. In this study, we investigated the effect of in vitro periodontal ligament cellular aging on the inflammatory cytokines, chemokines, and matrix metalloprotease(MMP)-2 expression induced by lipopolysaccharide(LPS) treatment. Three different cell populations were used; passages 4-5, 14-15, and 24-25 (at passage 27, more than 90% cells were replicative senescent). LPS increased the expression of interleukin(IL)-1${\beta}$, IL-6, and tumor necrosis factor-${\alpha}$, IL-8, RANTES, and MMP-2. However, the order of induction folds were passages 14-15 > 4-5 > 24-25. While the expression level of Toll-like receptor(TLR) 4 decreased according to the increase in passage number, the level of TLR2 was highest at passages 14-15 and then decreased at passages 24-25. While the spontaneous expression of IL-8 decreased according to the increase in passage number, that of RANTES and proMMP-2 increased according to the increase in passage number. These results suggest that the aging of periodontal ligament fibroblasts differentially affect the role as immunomodulatory cells in response to periodontopathic bacteria and therefore might be another risk factor of periodontitis progression.