• Molecules and Cells
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• 제23권2호
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• pp.198-206
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• 2007

Hydroquinone is a toxic compound and a major benzene metabolite. We report that it strongly inhibits the activation of macrophages and associated cells. Thus, it suppressed the production of proinflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-3, IL-6, IL-10, IL-12p40, IL-23], secretion of toxic molecules [nitric oxide (NO) and reactive oxygen species (ROS)] and the activation and expression of CD29 as judged by cell-cell adhesion and surface staining experiments. The inhibition was due to the induction of heme oxygenase (HO)-1 in LPS-activated macrophages, since blocking HO-1 activity with ZnPP, an HO-1 specific inhibitor, abolished hydroquinone's NO inhibitory activity. In addition, hydroquinone and inhibitors (wortmannin and LY294002) of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway had very similar inhibitory effects on LPS-induced and CD29-mediated macrophage responses, including the phoshorylation of Akt. Therefore, our data suggest that hydroquinone inhibits macrophage-mediated immune responses by modulating intracellular signaling and protective mechanisms.

• 약학회지
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• 제50권4호
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• pp.244-253
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• 2006

Effects of chrysene on immune functions were studied in female BALB/c mice. When mice were treated po with chrysene for 7 consecutive days, the antibody response was suppressed dose-dependently. Chrysene induced the enzyme activities of CYP LA and 2B time- and dose-dependently. In ex vivo lymphocyte proliferation, chrysene inhibited splenocyte proliferation by LPS and Con A. Moreover, the numbers of $CD4^+IL-2^+$ cells were reduced by chrysene. In conclusion, chrysene-induced immunotoxicity might be mediated, at least in part, via IL-2 production, and caused by mechanisms associated with metabolic activation.

• IMMUNE NETWORK
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• 제22권4호
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• pp.32.1-32.20
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• 2022

Sjögren syndrome (SS) is a chronic autoimmune disorder that primarily targets the salivary and lacrimal glands. The pathology of these exocrine glands is characterized by periductal focal lymphocytic infiltrates, and both T cell-mediated tissue injury and autoantibodies that interfere with the secretion process underlie glandular hypofunction. In addition to these adaptive mechanisms, multiple innate immune pathways are dysregulated, particularly in the salivary gland epithelium. Our understanding of the pathogenetic mechanisms of SS has substantially improved during the past decade. In contrast to viral infection, bacterial infection has never been considered in the pathogenesis of SS. In this review, oral dysbiosis associated with SS and evidence for bacterial infection of the salivary glands in SS were reviewed. In addition, the potential contributions of bacterial infection to innate activation of ductal epithelial cells, plasmacytoid dendritic cells, and B cells and to the breach of tolerance via bystander activation of autoreactive T cells and molecular mimicry were discussed. The added roles of bacteria may extend our understanding of the pathogenetic mechanisms and therapeutic approaches for this autoimmune exocrinopathy.

• 생약학회지
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• 제34권2호통권133호
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• pp.150-155
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• 2003

The nuclear factor of activated T cells (NFAT) protein induce transcription of cytokine genes required for T-cell activation, including the IL-2 gene. Activation of NFAT normally plays a significant role in inducing immune response. However, excessive activation provokes immunopathological reactions including autoimmunity, transplant rejection and inflammation. Thus, several natural products were screened on the inhibitory activity against the NFAT transcription factor. Among them, Euonymus sieboldiana showed strong inhibitory activity against the NFAT transcription factor without affecting cell viability.

• IMMUNE NETWORK
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• 제14권5호
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• pp.241-248
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• 2014

It is debatable whether AMP-activated protein kinase (AMPK) activation is involved in anti-apoptotic or pro-apoptotic signaling. AICAR treatment increases AMPK-${\alpha}1$ phosphorylation, decreases intracellular reactive oxygen species (ROS) levels, and significantly increases Annexin V-positive cells, DNA laddering, and caspase activity in human myeloid cell. AMPK activation is therefore implicated in apoptosis. However, AMPK-${\alpha}1$-knockdown THP-1 cells are more sensitive to apoptosis than control THP-1 cells are, suggesting that the apoptosis is AMPK-independent. Low doses of AICAR induce cell proliferation, whereas high doses of AICAR suppress cell proliferation. Moreover, these effects are significantly correlated with the downregulation of intracellular ROS, strongly suggesting that AICAR-induced apoptosis is critically associated with the inhibition of NADPH oxidase by AICAR. Collectively, our results demonstrate that in AICAR-induced apoptosis, intracellular ROS levels are far more relevant than AMPK activation.

• Journal of Microbiology
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• 제33권4호
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• pp.355-362
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• 1995

Induction of antibody production in C3H/He mice by bacterial infection is regulated through the processing exerted by antigen presenting cells. From the studies with Psudomonas aeruginosa, Salmonella typhimurium, and Micrococcus luteu, lipopolysaccharides (LPS) in Gram negative bacteria, which are known to be T-cell independent B cell mitogen, seem to be the major factor stimulating immune responses via activation of macrophages. Activation of macrophage, however, does not seem to correlate with antibody production. M. luteus was easily eliminatd by activated macrophages, while the processed antigens were immediately releasedd into culture medium before presentation. Nevertheless, antigens from Gram positive bacteria, Staphylococcus aureus and Bacillus subtilis, were very very active in chemotaxis and activation of periotoneal macrophages as well as in antien presnetation, while the very nature of the antigens is not yet clearly understood.

• 대한의생명과학회지
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• 제29권3호
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• pp.137-143
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• 2023

Inflammation plays an important role in immune system's response to tissue injury and biological stimuli. However, excessive inflammation can cause tissue damage. Therefore, the development of naturally derived anti-inflammatory agents have received broad attention. In this study, we investigated the anti-inflammatory mechanism of Rubi Fructus (RF) extract on the mast cell-mediated inflammatory response. To determine the regulatory mechanism of RF in inflammatory reaction, we evaluated the effects of RF on secretion of interleukin (IL)-8, IL-6 and tumor necrosis factor (TNF)-α and activation of nuclear factor-κB (NF-κB) and caspase-1 in activated human mast cells-1 (HMC-1). The results showed that RF attenuated IL-8, IL-6 and TNF-α secretion in a concentration-dependent manner. Moreover, RF significantly attenuated caspase-1and NF-κB activation in activated HMC-1. Conclusively, the present results provide evidence that RF may be a promising agent for anti-inflammatory therapy.

• Applied Biological Chemistry
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• 제48권3호
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• pp.246-251
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• 2005

본 시험은 면역계에서 중요한 역할을 담당하는 세포가운데 하나인 대식세포(Raw 264.7)를 게르마늄 강화 효모가 활성화시키는지 여부를 알아보기 위하여 대식세포의 배양액으로부터 NO와 $TNF-{\alpha}$의 생성을 in vitro 상에서 알아보고 iNOS의 발현 정도를 확인하고자 실시하였으며, 그 결과는 다음과 같다. 게르마늄 강화 효모 처리 후 세포 생존율(%)과 NO 생성량은 $10\;{\mu}g/ml$의 처리 농도에서 유의적으로 증가하였다(p < 0.05). 또한 NO 생성을 매개하는 iNOS의 발현 역시 $10\;{\mu}g/ml$의 농도에서 증가한 것으로 나타났다. 면역 및 항암 조절 인자로 알려진 $TNF-{\alpha}$의 생성 역시 농도 의존적으로 증가하였으며, $10\;{\mu}g/ml$의 처리 농도에서 유의적으로 증가하였다(p < 0.05). 이는 게르마늄 강화 효모가 항암 및 면역 증진 기능과 관련이 있는 $TNF-{\alpha}$ 분비를 촉진시키는데 영향을 준 것으로 사료된다. 따라서 본 시험 모델에서 게르마늄 강화 효모는 iNOS 발현을 조절하여 NO 및 $TNF-{\alpha}$의 생성을 매개하여 면역조절 기능에 도움을 줄 것으로 사료된다. 이것은 면역기능에 있어서 중요한 역할을 하는 대식세포를 활성화시켜 면역력을 활성화시키므로 세포성 면역의 활성화를 도모하고 손상된 면역 체계의 정상화에 영향을 주어 면역 강화 및 항암 예방 기능성 신소재로의 가능성을 지니는 것으로 사료된다.

• IMMUNE NETWORK
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• 제3권4호
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• pp.302-309
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• 2003

Background: CTLA4 (CD152), which is expressed on the surface of T cells following activation, has a much higher affinity for B7 molecules comparing to CD28, and is a negative regulator of T cell activation. In contrast to stimulating and agonistic capabilities of monoclonal antibodies specific to CTLA-4, CTLA4Ig fusion protein appears to act as CD28 antagonist and inhibits in vitro and in vivo T cell priming in variety of immunological conditions. We've set out to confirm whether inhibition of the CD28-B7 costimulatory response using a soluble form of human CTLA4Ig fusion protein would lead to persistent inhibition of alloreactive T cell activation. Methods: We have used CHO-$dhfr^-$ cell-line to produce CTLA4Ig fusion protein. After serum free culture of transfected cell line we purified this recombinant molecule by using protein A column. To confirm characterization of fusion protein, we carried out a series of Western blot, SDS-PAGE and silver staining analyses. We have also investigated the efficacy of CTLA4Ig in vitro such as mixed lymphocyte reaction (MLR) & cytotoxic T lymphocyte (CTL) response and in vivo such as experimental autoimmune encephalomyelitis (EAE), graft versus host disease (GVHD) and skin-graft whether this fusion protein could inhibit alloreactive T cell activation and lead to immunosuppression of activated T cell. Results: In vitro assay, CTLA4Ig fusion protein inhibited immune response in T cell-specific manner: 1) Human CTLA4Ig inhibited allogeneic stimulation in murine MLR; 2) CTLA4Ig prevented the specific killing activity of CTL. In vivo assay, human CTLA4Ig revealed the capacities to induce alloantigen-specific hyporesponsiveness in mouse model: 1) GVHD was efficiently blocked by dose-dependent manner; 2) Clinical score of EAE was significantly decreased compared to nomal control; 3) The time of skin-graft rejection was not different between CTLA4Ig treated and control group. Conclusion: Human CTLA4Ig suppress the T cell-mediated immune response and efficiently inhibit the EAE, GVHD in mouse model. The mechanism of T cell suppression by human CTLA4Ig fusion protein may be originated from the suppression of activity of cytotoxic T cell. Human CTLA4Ig could not suppress the rejection in mouse skin-graft, this finding suggests that other mechanism except the suppression of cytotoxic T cell may exist on the suppression of graft rejection.

• 대한한방부인과학회지
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• 제32권4호
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• pp.1-13
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• 2019

Objective: This study is aimed to investigate the anti-tumor metastasis by innate immunomodulating effects of crude polysaccharide isolated from Polygonati Rhizoma (CP-PR) on 4T1 breast cancer cells. Methods: CP-PR was isolated from Polygonati Rhizoma. Antimetastatic experiments were conducted in vivo mouse model by using 4T1 breast cancer cells. The cell viability of CP-PR was tested with normal spleen and 4T1 breast cancer cells. To observe the activation of macrophages with/without 4T1 breast cancer cells, production of tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), IL-10 and IL-12 were measured with enzyme-linked immunosorbent assay (ELISA), respectively. In addition, the lysis of YAC-1 cells and the production of granzymes were measured to observe the activation of natural killer (NK) cell. Results: Intravenous administration of CP-PR significantly inhibited metastasis of 4T1 breast cancer cells. In an in vitro cytotoxicity analysis, CP-PR affected the growth of normal spleen and 4T1 breast cancer cells above specific concentration. The production of $TNF-{\alpha}$, IL-6, IL-10 and IL-12 were significantly increased in macrophages with CP-PR. As compared with control, CP-PR showed significantly higher production of $TNF-{\alpha}$, IL-10 and IL-12 in macrophages co-cultured with 4T1 breast cancer cells. The lysis of YAC-1 cells and the production of granzymes were significantly up regulated by CP-PR. Conclusion: CP-PR appears to have considerable activity on the anti-metastasis by activation of innate immune system.