• Parasites, Hosts and Diseases
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• 제57권2호
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• pp.101-115
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• 2019

The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제18권1호
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• pp.153-163
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• 1996

Macrophage inflammatory protein $(MIP)-1{\alpha}$ is a cytokine which produces wide range of bioactivities such as proinflammatory, immunomodulatory, and hematopoietic modulatory actions. To determine whether $MIP-1{\alpha}$ acts as a negative regulator on the functions of lymphocyte, $[^3H]$-thymidine incorporation test and flow cytometric analysis were performed by using human tonsil T cell, human peripheral blood T cell, and murine cytolytic T lymphocyte (CTL) line CTLL-2, The results were as follow. 1. When human tonsil T lymphocytes were stimulated with anti-CD3 monoclonal antibody (mAb), rate of T cell proliferation was about four times increased. 200ng/ml of $MIP-1{\alpha}$ inhibited anti-CD3 mAb-mediated T cell growth as much as 60% (P<0.05). 2. The suppression of human peripheral T cell proliferation produced by $MIP-1{\alpha}$ was dramatic, but variable among T cells derived from different individuals $(40%{\sim}90%)$. 3. $MIP-1{\alpha}$inhibited the proliferation of murine CTL line CTLL-2 as much as 75%(P<0.001). 4. When the $MIP-1{\alpha}$ was added to human peripheral T cell, cell proporation of $CD4^+$ helper T cell and $CD8^+$ CTL were not noticeably affected. The expression level of CD4, not of Cd8, however, was down regulated by $MIP-1{\alpha}$ treatment $(27%{\sim}82%)$.

• 약학회지
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• 제51권1호
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• pp.35-43
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• 2007

To investigate the immunomodulatory roles of cyclic AMP (CAMP) on macrophage- and T lymphocyte-mediated immune responses, CAMP elevating agents were employed and carefully re-examined under the activation conditions of the cells. Various inhibitors tested dose-dependently blocked tumor necrosis factor (TNF)-${\alpha}$ production with IC$_{50}$ values ranged from 0.04 to 300 ${\mu}$M. Of the inhibitors, cAMP-elevating agents showed lower cytotoxicity assessed by lactate dehydrogenase (LDH) release, suggesting less toxic and more selective. In particular co-treatment of dbcAMP with a protein kinase C inhibitor staurosporine displayed the synergistic inhibition of TNF-${\alpha}$ production. The modulatory effect of dbcAMP on TNF-${\alpha}$ and nitric oxide (NO) was significantly affected by treatment time of dbcAMP. Thus, post-treatment of dbcAMP (three hours before LPS) abrogated dbcAMP's inhibitory activity and rather enhanced TNF-${\alpha}$ level up to 60%. In contrast, additional NO production was shown at the co-treatment of dbcAMP with LPS. Unlike simultaneous treatment of phorbol 12-myristate 13-acetate (PMA) and interferon (IFN)-${\gamma}$co-treatment, the combination of dbcAMP with other NO-inducing stimuli did not show drastic overproduction of NO. cAMP elevating agents also diminished splenocyte proliferation stimulated by concanavalin (Con) A, phytohemaglutinin A (PHA) and lipopolysaccharide (LPS). In addition, dbcAMP but not rolipram strongly suppressed CD8$^+$ T cells (CTLL-2). Finally, cAMP elevating agents were differentially involved in regulating CD98-mediated cell-cell adhesion. Thus, dbcAMP and rolipram significantly enhanced the cell-cell adhesion, whereas forskolin blocked. Therefore, our results suggest that CAMP elevating agents participate in various immune responses mediated by macrophages and T cells with a different fashion depending on cellular environments and activation signals.

• 생약학회지
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• 제31권1호
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• pp.7-15
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• 2000

Glycyrrhizae Radix aqua-acupuncture solution (GRAS) and Glycyrrhizae Radix water-extracted solution (GRWS) were prepared and tested for organ toxicities, antitumor activities, and immunomodulatory effects. The organ-toxicity of GRAS to male ICR mice was studied by the measurements of glutamic oxaloacetic transaminase (GOT), glutamic pyruvate transaminase (GPT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP-s) activities after injection of GRAS for 7 days. The activities of GOT, GPT, LDH, ALP-s were decreased with GRAS. It was shown to possess considerable toxicity toward various tumor cell lines. Concentration of GRAS at 1.5g/ml and 3g/ml resulted in more than 80% inhibition of growth in Ehrlich ascites tumor cells (EATC), Hepa1c1c7, and HeLa cells. Toxicity of GRAS to A549 revealed that 68% inhibition of growth. GRWS at the concentration of 3g/ml showed more than 80% inhibition of growth with EATC, Hepalclc7, A549 and HeLa. In morphological study, the number of cells were decreased, and the shape of cells was round-form in EATC, Hepalclc7, A549 and HeLa cells with GRAS. Administration of GRAS inhibited the growth of EATC in vivo. Mice given EATC at 1.5g/ml or 0.3g/ml GRAS had 16.7% to 50% survival after 21 days. GRAS increased the proliferation of T and B cells and the cytolytic activity of purified T cell. The biosyntheses of nucleic acid and protein of EATC, Hepalclc7, A549 and HeLa cells were inhibited by GRAS.

• IMMUNE NETWORK
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• 제10권4호
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• pp.126-134
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• 2010

Background: $CD8^+$ T cells contribute to the clearance of Hepatitis B virus (HBV) infection and an insufficient $CD8^+$ T cell response may be one of the major factors leading to chronic HBV infection. Since the HBx antigen of HBV can up-regulate cellular expression of several immunomodulatory molecules, we hypothesized that HBx expression in hepatocytes might affect $CD8^+$ T cell activity. Methods: We analyzed the activation and apoptosis of $CD8^+$ T cells co-cultured with primary hepatocytes rendered capable of expressing HBx by recombinant baculovirus infection. Results: Expression of HBx in hepatocytes induced low production of $interferon-{\gamma}$ and apoptosis of CD8+ T cells, with no effect on CD8 T cell proliferation. However, transcriptional levels of H-2K, ICAM-1 and PD-1 ligand did not correlate with HBx expression in hepatocytes. Conclusion: Our results suggest that HBx may inhibit $CD8^+$ T cell response by regulation of $interferon-{\gamma}$ production and apoptosis.

• Journal of Acupuncture Research
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• 제22권3호
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• pp.23-35
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• 2005

본 연구에서는 전침자극이 면역계의 THl/TH2 분화평형에 미치는 영향과 opioid system 과의 관계를 알아보고자 DNP-KLH의 자극을 통해 IgE 매개 알러지 반응모델을 구축하고 족삼리(足三里).에 전침자극을 가한 후 TH1/TH2 분화평형 및 opioid receptor antagonist인 naloxone에 의 한 반전여부를 확인하기 위해 total IgE, antigen-specific IgE, IFN-${\gamma}$ 및 IL-4 mRNA 발현량을 측정하여 다음과 같은 결과를 얻었다. 1. 전침자극은 DNP-KLH로 인해 과도하게 생산 된 혈청 total IgE 및 antigen-specific IgE를 감소시킴으로서 알러지 반응에 대한 유의한 억제능을 발휘하였으며, naloxone 투여로 전침 의 효과가 상쇠된 것으로 미루어 opioid system이 전침에 의한 항알러지 효과에 중요한 역할을 하는 것으로 추정된다. 2. 또한 전침자극은 DNP-KLH로 인한 TH2 cytokine의 편향상태에 대하여 TH1/TH2 평형조절능을 가진다는 것을 확인하였으며, naloxone으로 반전되지 않는 것으로 미루어 전침이 미치는 보조 T cell 분화에 대한 효과 는 opioid system에 의존하지 않는 것으로 추정된다.

• 한국약용작물학회지
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• 제17권4호
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• pp.273-279
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• 2009

GATA-binding protein-3 (GATA-3) and T-box expressed in T-cells (T-bet) are now considered as master transcription factors involving Th cell differentiation, but the roles of these factors are still uncertain in vivo. This study was conducted to investigate the expression of these transcription factors in the liver damage induced by carbon tetrachloride ($CCl_4$) in rats. In this study, liver damage were induced with Scutellaria baicalensis Georgi water extracts (SBW) and followed for 4 weeks. The expression of GATA-3 and T-bet protein in liver damage induced by $CCl_4$ and the serum levels of immunoglobulin A (IgA), IgE were studied after 4 weeks of treatment. We found that effect of SBW on IFN-$\gamma$, STAT1, pSTAT1 and T-bet was decreased in vivo. Several genes were demonstrated to be IL-4 inducible prior to the discovery of STAT6. $CCl_4$+SBW group was significantly lower than $CCl_4$ group in IL-4, STAT6, pSTAT6 and GATA-3. Our data indicate that cytokine protein production were increased in $CCl_4$ group and $CCl_4$+SBW group. From these results, water extracts obtained from Scutellaria baicalensis Georgi may have an immunoregulatory effect in the liver induced by $CCl_4$ of rats.

• 생약학회지
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• 제25권4호통권99호
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• pp.348-355
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• 1994

An antitumor component, F-D-P, was purified from the hot water extract of the carpophores of Elfvingia applanata by precipitation with ethanol, dialysis, and passage through a column of DEAE-cellulose ion exchange. F-D-P inhibited the growth of Sarcoma 180 in mice showing the tumor inhibition ratio of 88.3% in doses of 20 mg/kg for ten days. Chemical analysis of F-D-P showed that it was composed of polysaccharide(65.3%) and protein(6.5%0, and that the monosaccharides consisting of the polysaccharide was glucose(89.1%) and mannose(10.9%). The immunomodulatory activities of F-D-P were explored by determining its effect on the proliferation of the whole and subpopulations of lymphocytes, and on the generation of natural killer(NK) cell activity in vitro. F-D-P was mitogenic to total lymphocytes and B cells, but not to purified T cells, even in the presence of accessory cells. F-D-P did not increase NK cell activity when added to cultures of resting lymphocytes. From these results, it is clear that F-D-P modulates primarily the humoral immune responeses.

• 생명과학회지
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• 제24권12호
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• pp.1356-1363
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• 2014

28개의 아미노산으로 이루어져 있는 Ghrelin은 위 기저부의 X/A-유사 신경내분비 세포에서 주로 합성 분비되는 물질로 음식의 섭취나 비만, 에너지 항상성 등을 조절하는 역할을 하며, 이러한 Ghrelin 활성화는 수용체인 G-protein coupled growth hormone secretagogue receptor-1a (GHS-R1a)와 결합을 통해 일어난다. 최근 보고된 자료에 따르면, ghrelin과 수용체는 위나 시상하부, 뇌하수체 등뿐만 아니라 T 세포나 단핵구 및 대식세포 등 면역 세포에서도 생성되며, 염증반응을 유도하는 사이토카인의 생성을 억제하는 역할을 한다. 또한 흉선의 퇴화 등 면역기관에 있어서도 중요한 호르몬으로 보고되고 있지만 그 기전이나 기능에 대한 연구가 아직 미미한 실정이다. 본 연구에서는 흉선에서 T 세포의 성숙이나 세포활성을 억제하는 물질로 알려져 있는 덱사메타손(Dexamethasone; DEX)으로 세포사멸을 유도시킨 흉선세포에 ghrelin을 처리하여 세포사멸 억제효과를 알아보았다. 그 결과 Ghrelin은 세포사멸에 중요 단백질인 Caspase-3와 PARP 및 Bim의 활성화가 in vivo 및 in vitro 모두에서 효과적으로 저해됨을 확인할 수 있었으며, 이러한 세포사멸의 억제효과는 ghrelin을 처리할 경우 DEX에 의해 활성화된 Glucocorticoid 수용체(GR)의 인산화의 억제와 HSP90 등과 복합체를 이루고 있는 GR이 활성화되면서 분해되는 과정을 억제시켜 결과적으로 핵 안으로 이동하는 과정을 억제하는 기전을 통해 나타남을 알 수 있었다. 이러한 결과 등을 통해 볼 때, ghrelin은 약물이나 체내 생리적 스트레스 등으로 인해 발생하는 흉선 내 면역세포들의 세포사멸에 도움을 줄 것으로 사료되며, 나아가 이로 인한 흉선위축을 보호할 수 있는 치료 후보물질로서의 연구를 기대할 수 있으리라 사료된다.

• BMB Reports
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• 제44권7호
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• pp.462-467
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• 2011

Up-regulation of selected matrix metalloproteinases (MMPs) such as MMP-9 contributes to inflammatory processes during the development of various skin diseases, such as atopic dermatitis. In this study, we examined the effect of a cell-permeable superoxide dismutase (Tat-SOD) on TNF-${\alpha}$-induced MMP-9 expression in human keratinocyte cells (HaCaT). When Tat-SOD was added to the culture medium of HaCaT cells, it rapidly entered the cells in dose- and time-dependent manners. Tat-SOD decreased TNF-${\alpha}$-induced reactive oxygen species (ROS) generation. Tat-SOD also inhibited TNF-${\alpha}$-induced NF-${\kappa}B$ DNA binding activity. Treatment of HaCaT cells with Tat-SOD significantly inhibited TNF-${\alpha}$-induced mRNA and protein expression of MMP-9, as measured by RT-PCR and Western blot analysis. In addition, Tat-SOD suppressed TNF-${\alpha}$-induced gelatinolytic activity of MMP-9. Taken together, our results indicate that Tat-SOD can suppress TNF-${\alpha}$-induced MMP-9 expression via ROS-NF-${\kappa}B$-dependent mechanisms in keratinocytes, and therefore can be used as an immunomodulatory agent against inflammatory skin diseases related to oxidative stress.