• BMB Reports
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• v.55 no.1
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• pp.48-56
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• 2022

Small extracellular vesicles (sEVs) secreted by most cells carry bioactive macromolecules including proteins, lipids, and nucleic acids for intercellular communication. Given that some immune cell-derived sEVs exhibit anti-cancer properties, these sEVs have received scientific attention for the development of novel anti-cancer immunotherapeutic agents. In this paper, we reviewed the latest advances concerning the biological roles of immune cell-derived sEVs for cancer therapy. sEVs derived from immune cells including dendritic cells (DCs), T cells, natural-killer (NK) cells, and macrophages are good candidates for sEV-based cancer therapy. Besides their role of cancer vaccines, DC-shed sEVs activated cytotoxic lymphocytes and killed tumor cells. sEVs isolated from NK cells and chimeric antigen receptor (CAR) T cells exhibited cytotoxicity against cancer cells. sEVs derived from CD8⁺ T and CD4⁺ T cells inhibited cancer-associated cells in tumor microenvironment (TME) and activated B cells, respectively. M1-macrophage-derived sEVs induced M2 to M1 repolarization and also created a pro-inflammatory environment. Hence, these sEVs, via mono or combination therapy, could be considered in the treatment of cancer patients in the future. In addition, sEVs derived from cytokine-stimulated immune cells or sEV engineering could improve their anti-tumor potency.

• Korean Journal of Medicinal Crop Science
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• v.13 no.3
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• pp.87-92
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• 2005

The study was performed using of ethanol and water extracts of Fatsia japonica Decne. et Planch. in anticancer and immune activities. All extracts of 1.0 $g/{\ell}$ concentration were increased in over 60% of the anticancer activites in A549 and MCF7 cells. Root barks inhibited 55%, 74% in A549 and MCF7 cell by adding ethanol extracts of $g/{\ell}$ concentration. The cytotoxicity of human lung nomal cell (HEL299) counted up to about 22% for ethanol extracts of root barks in 1 $g/{\ell}$ concentration. The activity of human immune T and B cells were increased up to $140{\sim}170%$ by adding ethanol extract of the root barks. Increasing trend of secretion of cytokine (IL-6, $TNF-{\alpha}$) from human B and T cell for 5 days cultivation has been abserved. From the results, the anticancer and immune-stimulatory activities of the roots extract were higher than the extracts of other parts.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.11
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• pp.1592-1597
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• 2013

Type of dietary direct-fed microbials (DFMs) or poultry litter could directly influence the composition of gut microbiota. Gut microbiota plays an important role in shaping the developing immune system and maintaining the homeostasis of the mature immune system in mammal and chickens. The present study was carried out to investigate the interaction among litter, DFMs and immunity in broiler chickens exposed to a field-simulated environment. Immune status of broiler chickens was assessed by serum antibodies against Eimeria spp. and Clostridium spp. and intestinal cytokine mRNA expression. The current experimental design had a $3{\times}2$ factorial arrangement of treatments with three types of litter, i.e., fresh litter or used litter that was obtained from a farm with no disease outbreak (used litter) or a farm with history of a gangrenous dermatitis outbreak (GD litter), and two dietary treatments with or without DFMs. It was found that either DFM addition or type of litter significantly affected anticoccidial antibody levels of broiler chickens at d 42. In general, dietary DFMs increased the anticoccidial antibodies in the fresh-litter raised chickens, but lowered the levels in the GD-litter raised chickens. Serum antibodies against Clostridium perfringens ${\alpha}$-toxin were significantly (p<0.05) higher in chickens raised on GD litter compared with those raised on fresh litter. Cytokine mRNA expression was significantly (p<0.05) altered by either the type of litter or DFMs. Of interest, dietary DFMs lowered interferon-${\gamma}$, interleukin 1beta, and CXCLi2 cytokine mRNA expression in chickens raised on fresh litter but increased them in GD-litter raised chickens. In conclusion, dietary DFMs modulate various immune parameters of broiler chickens, but the DFM-mediated effects were dependent upon the type of litter on which chickens were raised.

• IMMUNE NETWORK
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• v.9 no.5
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• pp.158-168
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• 2009

Tumor therapy using cytokines has been developed for last two decades. Several recombinant cytokines and tumor cell vaccines produced by cytokine gene transfer have been in clinical trials, but several side effects hamper routine clinical applications. Many cytokines are originally expressed as membrane-bound form and then processed to secretory form exerting paracrine effects. Though functional differences of these two types of cytokines are elusive yet, the membrane-bound form of cytokine may exert its effects on restricted target cells as a juxtacrine, which are in physical contacts. With the efforts to improve antitumor activities of cytokines in cancer patients, developing new strategies to alleviate life-threatening side effects became an inevitable goal of tumor immunologists. Among these, tumor cell vaccines expressing cytokines as membrane-bound form on tumor cell surface have been developed by genetic engineering techniques with the hope of selective stimulation of the target cells that are in cell-to-cell contacts. In this review, recent progress of tumor cell vaccines expressing membrane-bound form of cytokines will be discussed.

• Journal of Ginseng Research
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• v.20 no.1
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• pp.15-22
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• 1996

In order to investigate the Immunomodulatory effects of ginseng, we have studied the effects of ginseng saponin on the proliferation and cytosine gene expression of human pheripheral blood mononuclear cell (PBMC). In the PBMC proliferation assay, total saponin exhibited proliferation inhibition on the PBMC or phytohemagglutinin(PHA)-stimulated PBMC in a dose-dependent fashion. Immunomodulatory effects of ginseng were further investigated using the cytokine gene expression as the indicators. In the reverse transcription-polymerase chain reaction (RT-PCR) test, interleukin (IL)-1, IL-2, IL-3, IL-4, IL-6, IL-13, granulocyte macrophage-colony stimulating factor, tumor necrosis factor (TNF), migration inhibitory factor and transforming growth factor genes were expressed in the PHA-stimulated PBMC 48 hrs after cell culture. Among expressed cytokines, total saponin could increase the expression of IL-1 and TNF of PBMC without stimulation of PHA. All of ginsenosides, $Rb_1$, $Rb_2$, $Rg_1$, Rc, Re, incresed TNF gene expression. Especially, Rb2 (20 g/ml) showed most prominent effect on TNF gene expression and it also slightly increased IL-1 gene expression of PBMC.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.622-626
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• 2023

The COVID-19 pandemic has changed the world and has presented the scientific community with unprecedented challenges. Infection is associated with overproduction of proinflammatory cytokines secondary to hyperactivation of the innate immune response, inducing a cytokine storm and triggering multiorgan failure and significant morbidity/mortality. No specific treatment is yet available. For thousands of years, Panax notoginseng has been used to treat various infectious diseases. Experimental evidence of P. notoginseng utility in terms of alleviating the cytokine storm, especially the cascade, and improving post-COVID-19 symptoms, suggests that P. notoginseng may serve as a valuable adjunct treatment for COVID-19 infection.

• International Journal of Industrial Entomology and Biomaterials
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• v.12 no.2
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• pp.57-61
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• 2006

Suppressor of cytokine signaling (SOCS) is known to be as a negative feedback regulator in Janus kinase signal transducer and activator of transcription signaling. Highly conserved SOCS box domain was cloned from a Korean malaria vector, Anopheles sinensis. Sequence analysis indicates that it has identity to Anopheles gambiae (96%), Aedes aegypti (94%), Drosophila melanogaster (78%), Mus musculus (72%) and Homo sapiens (72%), respectively. Tissue specificity RT-PCR demonstrated that the expression level of AsSOCS transcript was high at abdomen, midgut, and ovary, whereas developmental expression patterns showed that the level of AsSOCS was high at egg, early pupae, and adult female. On the other hand, RT-PCR analysis after bacterial challenge showed that SOCS mRNA was strongly induced in larvae. In addition, it was also induced by various immune elicitors such as lipoteicoic acid, CpG-DNA, and laminarin. It seems that AsSOCS, repressor of JAK-STAT pathway, is highly conserved in mosquito, and may play an important role in mosquito innate immune response.

• IMMUNE NETWORK
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• v.11 no.3
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• pp.169-174
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• 2011

Background: NADPH oxidase (NOX) modulates cell proliferation, differentiation and immune response through generation of reactive oxygen species. Particularly, NOX2 is recently reported to be important for regulating Treg cell differentiation of CD4+ T cells. Methods: We employed ovalbumin-induced airway inflammation in wild-type and NOX2-deficient mice and analyzed tissue histopathology and cytokine profiles. Results: We investigated whether NOX2-deficiency affects T cell-mediated airway inflammation. Ovalbumin injection which activates T cell-mediated allergic response increased airway inflammation in wild-type mice, as evidenced by increased immune cell infiltration, allergic cytokine expression, and goblet cell hyperplasia in the lung. Interestingly, NOX2 knockout (KO) mice were more susceptible to allergen-induced lung inflammation compared to wild-type mice. Immune cells including neutrophils, lymphocytes, macrophages, and eosinophils were drastically infiltrated into the lung of NOX2 KO mice and mucus secretion was substantially increased in deficiency of NOX2. Furthermore, inflammatory allergic cytokines and eotaxin were significantly elevated in NOX2 KO mice, in accordance with enhanced generation of inflammatory cytokines interleukin-17 and interferon-${\gamma}$ by CD4+ T cells. Conclusion: These results indicate that NOX2 deficiency favorably produces inflammatory cytokines by T cells and thus increases the susceptibility to severe airway inflammation.

• Parasites, Hosts and Diseases
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• v.55 no.4
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• pp.375-384
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• 2017

Trichomonas vaginalis is a pathogen that triggers severe immune responses in hosts. T. vaginalis ${\alpha}$-actinin 2, $Tv{\alpha}$-actinin 2, has been used to diagnose trichomoniasis. This study was undertaken to examine the role of $Tv{\alpha}$-actinin 2 as an antigenic molecule to induce immune responses from humans. Western blot analysis using anti-$Tv{\alpha}$-actinin 2 antibodies indicated its presence in the secreted proteins of T. vaginalis. ELISA was employed to measure cytokine production by vaginal epithelial cells, prostate cells, mouse dendritic cells (DCs), or T cells stimulated with T. vaginalis or $Tv{\alpha}$-actinin 2 protein. Both T. vaginalis and $rTv{\alpha}$-actinin 2 induced cytokine production from epithelial cell lines, including IL-10. Moreover, $CD4^+CD25^-$ regulatory T cells (Treg cells) incubated with $rTv{\alpha}$-actinin 2-treated DCs produced high levels of IL-10. These data indicate that $Tv{\alpha}$-actinin 2 modulates immune responses via IL-10 production by Treg cells.

• Journal of Microbiology and Biotechnology
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• v.26 no.7
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• pp.1198-1205
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• 2016

Lactic acid bacteria (LAB) have beneficial effects on intestinal health and skin diseases. Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is known to induce the production of several cytokines such as TNF-α, IL-1β, and IL-8 and affect the intestinal microflora, anti-aging, sepsis, and cholesterol level. In this study, Weissella cibaria was isolated from Indian dairy products, and we examined its immune-enhancing effects. Live and heat-killed W. cibaria did not induce the secretion of immune-related cytokines, whereas LTA isolated from W. cibaria (cLTA) significantly increased the secretion of TNF-α, IL-1β, and IL-6 in a dose-dependent manner. cLTA increased the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells, p38 mitogen-activated protein kinases, and c-Jun N-terminal kinases in THP-1 cells. The secretion of TNF-α and IL-6 was also increased in the cLTA-treated mouse splenocytes. These results suggest that cLTA, but not W. cibaria whole cells, has immune-boosting potential and can be used to treat immunosuppression diseases.