• 대한본초학회지
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• 제26권4호
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• pp.187-194
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• 2011

Objective : Astragali Radix (AR) and Cinnamomi Cortex (CC) are used to enhance immune response in Asian traditional medicine. Immuno-potentiation of the combination of AR and CC were evaluated on the cellular and humoral immune response using murine macrophage cell line (RAW 264.7) and OVA-immunized mice. Methods : This study was designed to investigate the immuno-potentiative effects of AR, CC, and AR with CC on nitric oxide synthesis in RAW 264.7 cells and proliferation and production levels of Intereukin-2 (IL-2) in mouse splenocytes. In addition, we evaluated the plasma-specific antibody responses and splenocyte proliferation on ovalbumin (OVA)-immunized mice treated with herbal extracts. Results : Combination treatment with AR and CC increased nitric oxide synthesis in RAW 264.7 cells and IL-2 level in splenocytes (p<0.001). Combination of AR and CC significantly enhanced the Concanavalin A- (Con A ; T cell mitogen) and lipopolysaccharide-(LPS ; B cell mitogen) induced splenocyte proliferation on the OVA-immunized mice. Combination of AR and CC also significantly enhanced plasma levels of OVA-specific IgG (p<0.01), IgG1 (p<0.05) and total IgM (p<0.01) compared with the OVA-immunized control group. Conclusion : These results suggest that combination of AR and CC could be used as therapeutic profile on activation of immune response.

• Molecules and Cells
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• 제44권6호
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• pp.408-421
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• 2021

The outbreak of coronavirus disease 2019 (COVID-19) has not only affected human health but also diverted the focus of research and derailed the world economy over the past year. Recently, vaccination against COVID-19 has begun, but further studies on effective therapeutic agents are still needed. The severity of COVID-19 is attributable to several factors such as the dysfunctional host immune response manifested by uncontrolled viral replication, type I interferon suppression, and release of impaired cytokines by the infected resident and recruited cells. Due to the evolving pathophysiology and direct involvement of the host immune system in COVID-19, the use of immune-modulating drugs is still challenging. For the use of immune-modulating drugs in severe COVID-19, it is important to balance the fight between the aggravated immune system and suppression of immune defense against the virus that causes secondary infection. In addition, the interplaying events that occur during virus-host interactions, such as activation of the host immune system, immune evasion mechanism of the virus, and manifestation of different stages of COVID-19, are disjunctive and require thorough streamlining. This review provides an update on the immunotherapeutic interventions implemented to combat COVID-19 along with the understanding of molecular aspects of the immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may provide opportunities to develop more effective and promising therapeutics.

• Parasites, Hosts and Diseases
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• 제56권4호
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• pp.325-334
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• 2018

Toxoplasma gondii is an apicomplexan zoonotic protozoan parasite that infects most species of warm-blooded animals, including humans. The heavy incidence and severe or lethal damage caused by T. gondii infection clearly indicate a need for the development of an effective vaccine. T. gondii GRA8 is a member of the dense granules protein family and is used as a marker of acute infection. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pDsRed2-GRA8, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with the pDsRed2-GRA8 plasmid and then challenged by infection with the highly virulent GFP-RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii of this vaccine were analyzed by measuring cytokine and serum antibody titers, splenocyte proliferation assays, and the survival times of mice after challenge. Our results showed that mice immunized with pDsRed2-GRA8 demonstrated specific humoral and cellular responses, induced higher IgG antibody titers with predominant IgG2a production; increased levels of IL-10, IL-12 (p70), $IFN-{\gamma}$, $TNF-{\alpha}$, and splenocyte proliferation; and prolonged survival times compared to those of control mice. The present study showed that DNA immunization with pDsRed2-GRA8 induced humoral and cellular immune responses, and all immunized mice showed greater Th1-type immune responses and longer survival times than those of control mice. These results indicated that T. gondii GRA8 DNA immunization induces a partial protective effect against acute toxoplasmosis.

• 대한간호학회지
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• 제23권4호
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• pp.528-543
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• 1993

Vitamin E, which has its advocates in the treatment of diabetes mellitus. autoimmune disease, cancer and peripheral vascular and thromboembolic disease, has now been alleged to have a powerful antioxident effect and to affect various biological activities such as fertility factor, inhibition of human platelet aggregation and stabilization of biological membranes. The present study was designed to test whether vitamin I(alpha-tocopherol) can : (1) enhance the hemagglutinin response to sheep red blood cells (SRBC), (2) modulate Arthus and delayed type hypersensitivity(DTH) to SRBC and contact hypersensitivity to dinitrofluorobenzene (DNFB). (3) enhance the mitogenic response of murine splenocyte, (4) decrease the recovery of Cryptococcus neoformans from brain, lung, liver, spleen and kidney of infected mice and (5) have an inhibitory or enhancing effect on the induction of active systemic anaphylaxis(ASA) induced by chicken-gamma globulin (CGG) in mice. Mice were given either intramuscular injections of 0.3ml (300mg) of vitamin I before immunization or were infection for 10 consecutive days or were given by vitamin I esophageal intubation, 0.1ml(100mg), for 20 days before sacrifice for the mitogenic response experiments. It was found that vitamin E treated mice showed a significant enhancement in hemagglutinin response, Arthus reaction and DTH to SRBC and contact hypersensitivity to DNFB. There was no significant difference in the mitogenic response to phytohemagglutinin(PHA), but the response to concanavalin A(ConA) or pokeweed mitogem(PWM) was increased in vitamin E-treated mice. Interestingly, the vitamin E administration before C. neoformans infection decreased significantly the recovery of C. neoformans from brain lung, liver, spleen and kidney of the infected mice as compared with that of the control mice, strongly suggesting that vitamin E pretreatment may increase the resistance of mice to the fungal infection. Unexpectedly, vitamin E administration enhanced the production of CGG -induced ASA. Taken together, it can be concluded that vitamin I administration may in-crease the humoral and cellular immune response and resistance. to C. neoformans infection, but enhance the induction of ASA to CGG. Further studies are necessary to clarify the underlying mechanism accounting for these effects.

• Molecules and Cells
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• 제40권3호
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• pp.163-168
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• 2017

Microglia are the primary resident immune cells of the central nervous system (CNS). They are the first line of defense of the brain's innate immune response against infection, injury, and diseases. Microglia respond to extracellular signals and engulf unwanted neuronal debris by phagocytosis, thereby maintaining normal cellular homeostasis in the CNS. Pathological stimuli such as neuronal injury induce transformation and activation of resting microglia with ramified morphology into a motile amoeboid form and activated microglia chemotax toward lesion site. This review outlines the current research on microglial activation and chemotaxis.

• Molecules and Cells
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• 제43권1호
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• pp.10-22
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• 2020

Mitochondria have several quality control mechanisms by which they maintain cellular homeostasis and ensure that the molecular machinery is protected from stress. Mitophagy, selective autophagy of mitochondria, promotes mitochondrial quality control by inducing clearance of damaged mitochondria via the autophagic machinery. Accumulating evidence suggests that mitophagy is modulated by various microbial components in an attempt to affect the innate immune response to infection. In addition, mitophagy plays a key role in the regulation of inflammatory signaling, and mitochondrial danger signals such as mitochondrial DNA translocated into the cytosol can lead to exaggerated inflammatory responses. In this review, we present current knowledge on the functional aspects of mitophagy and its crosstalk with innate immune signaling during infection. A deeper understanding of the role of mitophagy could facilitate the development of more effective therapeutic strategies against various infections.

• IMMUNE NETWORK
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• 제22권1호
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• pp.5.1-5.22
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• 2022

The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

• Bulletin of the Korean Chemical Society
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• 제32권11호
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• pp.3893-3898
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• 2011

Cellular uptake of double-stranded DNA (dsDNA) triggers strong innate immune responses via activation of NF-${\kappa}B$ transcription factor. However, the detailed mechanism of dsDNA-mediated innate immune response remains yet to be elucidated. Here, we show that the expression of tazarotene-induced gene 3 (TIG3) is dramatically induced by dsDNA stimulation, and the siRNA-mediated down-regulation of TIG3 mRNA results in significant suppression of dsDNA-triggered cytokine expression. Because TIG3 has been previously shown to physically interact with transglutaminase (TG) 1 to activate TG activity, and TG2 has been shown to induce NF-${\kappa}B$ activity by inducing $I{\kappa}B{\alpha}$ polymerization, we tested whether TG also plays a role in dsDNA-mediated innate immune response. Pre-treatment of TG inhibitors dramatically reduces dsDNA-triggered cytokine induction. We also show that, in HeLa cells, TG2 is the major TG, and TIG3 physically interacts with TG2. Combined together, our results suggest a novel mechanism of dsDNA-triggered innate immune response which is critically dependent on TIG3 and TG2.

• Molecules and Cells
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• 제38권2호
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• pp.112-121
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• 2015

Ectopic expression of $14-3-3{\zeta}$ has been found in various malignancies, including lung cancer, liver cancer, head and neck squamous cell carcinoma (HNSCC), and so on. However, the effect of $14-3-3{\zeta}$ in the regulation of interactions between tumor cells and the immune system has not been previously reported. In this study, we aimed to investigate whether and how $14-3-3{\zeta}$ is implicated in tumor inflammation modulation and immune recognition evasion. In oral squamous cell carcinoma (OSCC) cell lines and cancer tissues, we found that $14-3-3{\zeta}$ is overexpressed. In OSCC cells, $14-3-3{\zeta}$ knockdown resulted in the up-regulated expression of inflammatory cytokines. In contrast, $14-3-3{\zeta}$ introduction attenuated cytokine expression in human normal keratinocytes and fibroblasts stimulated with interferon-${\gamma}$ (IFN-${\gamma}$) and lipopolysaccharide (LPS). Furthermore, supernatants from $14-3-3{\zeta}$ knockdown OSCC cells dramatically altered the response of peritoneal macrophages, dendritic cells and tumor-specific T cells. Interestingly, Stat3 was found to directly interact with $14-3-3{\zeta}$ and its disruption relieved the inhibition induced by $14-3-3{\zeta}$ in tumor inflammation. Taken together, our studies provide evidence that $14-3-3{\zeta}$ may regulate tumor inflammation and immune response through Stat3 signaling in OSCC.

• Biomolecules & Therapeutics
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• 제8권2호
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• pp.199-205
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• 2000

On the inter-order protoplast fusants of Lentinus edodes and Ganoderma lucidum was the antitumor activity test performed and the fusant P22 was selected. The hot water extract of the cultured mycelia of P22 were purified by DEAE-cellulose chromatographya and the resulting purified fraction was designated as P22A. It was found to be a proteoglycan whose molecular weight was 47 kDa. When examined for immunopotentiation activity, P22A increased the number of colony forming unit in the bone marrow stem cells to 3-folds. It also potentiated the secretion of nitric oxide in activated macrophages to 2-folds. In humoral immune response, it increased the activities of the alkaline phosphatase in differentiated B cells to 1.6-folds and the number of plaque forming cells to 1.8-folds. In cellular immune response, it restored the depressed response of delayed type hypersensitivity in tumor bearing mice to normal level. These results suggest that P22A have potential to restore the decreased immune activity of the tumor bearing mice to normal level.