• IMMUNE NETWORK
• /
• 제10권3호
• /
• pp.92-98
• /
• 2010

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs). Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells. Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs. Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

• Molecules and Cells
• /
• 제39권8호
• /
• pp.631-638
• /
• 2016

Glutathione peroxidase 3 (GPx3), an antioxidant enzyme, acts as a modulator of redox signaling, has immunomodulatory function, and catalyzes the detoxification of reactive oxygen species (ROS). GPx3 has been identified as a tumor suppressor in many cancers. Although hyper-methylation of the GPx3 promoter has been shown to down-regulate its expression, other mechanisms by which GPx3 expression is regulated have not been reported. The aim of this study was to further elucidate the mechanisms of GPx3 regulation. GPx3 gene analysis predicted the presence of ten glucocorticoid response elements (GREs) on the GPx3 gene. This result prompted us to investigate whether GPx3 expression is regulated by the glucocorticoid receptor (GR), which is implicated in tumor response to chemotherapy. The corticosteroid dexamethasone (Dex) was used to examine the possible relationship between GR and GPx3 expression. Dex significantly induced GPx3 expression in H1299, H1650, and H1975 cell lines, which exhibit low levels of GPx3 expression under normal conditions. The results of EMSA and ChIP-PCR suggest that GR binds directly to GRE 6 and 7, both of which are located near the GPx3 promoter. Assessment of GPx3 transcription efficiency using a luciferase reporter system showed that blocking formation of the GR-GRE complexes reduced luciferase activity by 7-8-fold. Suppression of GR expression by siRNA transfection also induced down-regulation of GPx3. These data indicate that GPx3 expression can be regulated independently via epigenetic or GR-mediated mechanisms in lung cancer cells, and suggest that GPx3 could potentiate glucocorticoid (GC)-mediated anti-infla-mmatory signaling in lung cancer cells.

• Archives of Pharmacal Research
• /
• 제26권4호
• /
• pp.294-300
• /
• 2003

A polysaccharide fraction, AIP1, purified from Artemisia iwayomogi was shown to have immunomodulating and anti-tumor activities in mice. In order to determine how the AIP1 fraction exhibits the immunomodulating activity, the effect of the fraction on the apoptosis of mouse spleen cells was investigated. Treatment of the mouse spleen cells with the AIP1 fraction resulted ,in the suppression of apoptotic death and an extension of cell survival in culture, indicating that the fraction might modulate the death of spleen cells. Treatment of the mice with the AIP1 fraction in vivo also resulted in less apoptosis of the spleen cells, which indicates the physiological relevance of the anti-apoptosis effect of the fraction in vitro. A mouse gene array was used to determine the profile of the gene expression change showing a pattern of up- and down-regulated genes by the AIP1 treatment. This study provides preliminary information regarding the immunomodulatory mechanism of the AIP1 fraction.

• 대한수의학회지
• /
• 제55권1호
• /
• pp.21-30
• /
• 2015

The immune system is specifically sensitive to oxidative stress induced by ionizing radiation because of its rapid proliferative activity. For this reason, an instructive immune system is one of the best ways to minimize side effects, such immunodeficiency, of gamma radiation. Over the past few decades, several natural plants with antioxidant and immunomodulatory properties have been identified as adjuncts for nontoxic and successful radiotherapy. Hizikia fusiforme extract (HFE) containing plentiful dietary fiber and fucoidan is known for its instructive antioxidant capacity, immunomodulation abilities, and immune activation. In this study, we determined whether HFE protects radiosensitive immune cells from gamma radiation-induced damage. C57BL/6 mice were irradiated with gamma-ray. The effect of HFE on the ionizing radiation damage of immune cells was then evaluated with an MTT assay, 3H-thymidine incorporation assay, and PI staining. We found that HFE stimulated the proliferation of gamma-ray irradiated immune cells without cytotoxic effects. We also observed that HFE not only decreased DNA damage but also reduced gamma radiation-induced apoptosis of the immune cells. Our results suggest that HFE can protect immune cells from gamma-ray damage and may serve as an effective, non-toxic radioprotective agent.

• Asian-Australasian Journal of Animal Sciences
• /
• 제33권11호
• /
• pp.1797-1808
• /
• 2020

Objective: This study assessed the effects of probiotics on cecal microbiota, gene expression of intestinal tight junction proteins, and immune response in the cecal tonsil of broiler chickens challenged with Salmonella enterica subsp. enterica. Methods: One-day-old broiler chickens (n = 240) were randomly allocated to four treatments: negative control (Cont), multi-strain probiotic-treated group (Pro), Salmonella-infected group (Sal), and multi-strain probiotic-treated and Salmonella-infected group (ProSal). All chickens except those in the Cont and Pro groups were gavaged with 1×10⁸ cfu/mL of S. enterica subsp. enterica 4 days after hatching. Results: Our results indicated that body weight, weight gain, and feed conversion ratio of birds were significantly reduced (p<0.05) by Salmonella challenge. Chickens challenged with Salmonella decreased cecal microbial diversity. Chickens in the Sal group exhibited abundant Proteobacteria than those in the Cont, Pro, and ProSal groups. Salmonella infection downregulated gene expression of Occludin, zonula occludens-1 (ZO1), and Mucin 2 in the jejunum and Occludin and Claudin in the ileum. Moreover, the Sal group increased gene expression of interferon-γ (IFN-γ), interleukin-6 (IL-6), IL-1β, and lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF) and reduced levels of transforming growth factor-β4 and IL-10 compared with the other groups (p<0.05). However, chickens receiving probiotic diets increased Lactobacillaceae abundance and reduced Enterobacteriaceae abundance in the ceca. Moreover, supplementation with probiotics increased the mRNA expression of Occludin, ZO1, and Mucin 2 in the ileum (p<0.05). In addition, probiotic supplementation downregulated the mRNA levels of IFN-γ (p<0.05) and LITAF (p = 0.075) and upregulated IL-10 (p = 0.084) expression in the cecal tonsil. Conclusion: The administration of multi-strain probiotics modulated intestinal microbiota, gene expression of tight junction proteins, and immunomodulatory activity in broiler chickens.

• Nutrition Research and Practice
• /
• 제8권4호
• /
• pp.386-390
• /
• 2014

BACKGROUND: Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity. MATERIALS/METHODS: We investigated the effects of ADA extract on two mouse models of Alzheimer's disease (AD); intracerebroventricular injection of ${\beta}$-amyloid peptide ($A{\beta}$) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice. RESULTS: Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of $A{\beta}1$-42 until evaluation) effectively blocked $A{\beta}1$-42-induced impairment in passive avoidance performance, and $A{\beta}1$-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-$1{\alpha}$ in the hippocampus. In addition, it alleviated the $A{\beta}1$-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-$1{\beta}$ in the brain. CONCLUSIONS: The results of this study suggest that ADA stem extract may be useful for prevention and treatment of AD.

• IMMUNE NETWORK
• /
• 제15권3호
• /
• pp.150-160
• /
• 2015

We previously reported that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) accelerates hematopoiesis and has an improving effect on animal disease models such as sepsis and asthma. The effects of PLAG supplementation on immune modulation were assessed in healthy men and women. The objective was to evaluate the effects of PLAG supplementation on immune regulatory functions such as activities of immune cells and cytokine production. A randomized double blind placebo-controlled trial was conducted. Seventy-five participants were assigned to one of two groups; all participants had an appropriate number of white blood cells on the testing day. The PLAG group (n=27) received oral PLAG supplements and the control group (n=22) received oral soybean oil supplements. IL-4 and IL-6 production by peripheral blood mononuclear cells (PBMC) were lower (p<0.001 and p<0.001, respectively) with PLAG than with soybean oil. However, the production of IL-2 and IFN-$\gamma$ by PBMC was unaltered with PLAG supplementation. The B cell proliferation decreased significantly in the PLAG group compared to the soybean oil control (p<0.05). The intake of PLAG in healthy adults for 4 weeks was deemed safe. These data suggest that PLAG has an immunomodulatory function that inhibits the excessive immune activity of immunological disorders such as atopic and autoimmune diseases. PLAG could improve the condition of these diseases safely as a health food supplement.

• 한국임상수의학회지
• /
• 제15권2호
• /
• pp.346-351
• /
• 1998

As an antitumor agents cyclophosphamide (CPA) is frequently used in animal clinic. Important adverse effects of its administration are leukopenia, thrombocytopenia and anemia. We investigated the effects of chicken egg white derivatives (EWD and EF-203) on the changes of blood cells and the neutrophil phagocytosis of rats administered with CPA. Rats were administered CPA peritoneally at dose of 50 mgag once a day far 3 days plus either EWD or EF-203 orally at dose of 200 mg/kg once a day far 3 days. Thereafterl the changes of blood cells by automatic blood cell counter and the phagocytosis of neutrophils by flow cytometry were examined far 7 days. There was no change in RBC values regardless of administration of either EWD or EF-203 throughout experimental period. But rats receiving CPA plus either EWD or EF-203 showed a significant higher PCV values than those of CPA alone (p<0.01). The numbers of peripheral blood platelets and WBC and the differential count of neutrophils in the ra% receiving CPA plus either EWD or EF-203 were significantly higher (p<0.05 to 0.01) than those of CPA alone. Moreover, these rats showed significanly enhanced phagocytoses of neutrophils when compared to rats with CPA alone (p<0.01). These result suggested that chicken egg white derivatives including EWD and EF-2% have immunomodulatory effects in regard to the increase of platelets, WBC, differential count of neutrophils, PCV, and the enhancement of phagocytic activity of neutrophils in immunosuppressed rats by CPA. Thus, co-adminstration of chicken egg white derivatives will be able to reduce the side effects in the animals treated with antitumor agents.

• 한국식품과학회지
• /
• 제36권6호
• /
• pp.986-990
• /
• 2004

대식세포는 IL-1, IL-6, $TNF-{\alpha},\;IFN-{\gamma}$의 중요한 근원이고, 전염성의 병원체와 종양 세포에 대해 저항하는 주요한 effector 세포이다. 이것은 cytokine signal에 의해 세포파괴가 되도록 활성화 된다. 이번 연구에서 우리는 산더덕의 물 추출물이 cytokine, nitric oxide와 같은 effector 분자를 유도하기 위해 대식세포를 활성화하는지를 알아보기 위하여 실험하였다. 산더덕 추출물에 의한 대식세포의 NO 생성은 농도 의존적이고, 시간 의존적이었다. iNOS는 시간이 지날수록 발현이 유도되었다. 산더덕 추출물에 의한 IL-1과 IL-6 mRNA 유도는 시간 의존적으로 증가 되었고, 처리 후 24시간에 최고점에 도달하였다. 이것은 활성화된 대식세포가 종양세포를 죽일 수 있음을 말한다. $TNF-{\alpha}\;mRNA$의 양은 시간이 지나도 일정하였고, $IFN-{\gamma}\;mRNA$의 양은 산더덕 추출물의 처리 1시간 후에 빠르게 강화되었다. 이러한 결과로부터 산더덕은 효과적인 면역조절자이고 대식세포의 항종양활성을 강화함을 알 수 있다.

• 대한한의학방제학회지
• /
• 제5권1호
• /
• pp.147-168
• /
• 1997

Tish study was carried out to evaluate the possible therapeutic or antitumoral effects of Takrisodokyeum extract against tumor, and immunomodulatory effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene (MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S-I80 and Fas II cells). Treatment of the Takrisodokyeum water-extract(daily 1mg mouse, i.p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 15 days. Against squamous cell carcinoma induced by MCA, Takrisodokyeum decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice (TBM). Takrisodokyeum also significantly suppressed the development of 3LLcell and S-180 cell by frequency and their size, and some developed tumors were regressed by the continuous treatment of Takrisodokyeum extract into TBM. However, when tumor was induced by FsaII cell-implantation, the growth of implanted cells in mice was delayed by the water extract of Takrisodokyeum until day 7 and then rapid growth ensued. In vitro, treatment of Takrisodokyeum extract had no effect on the growth of some kind of cell lines such as FsaII, A-131 strain but significantly inhibited the proliferation of 3LL, S-180 cells. Takrisodokyeum also stimulated the migrative ability of leucocyte, the MIF and IL 2-production of T lymphocytes, but not IL 6 production of B cells. Takrisodokyeum enhanced Arthus reaction and DTH to sheep erythrocytes, and NK cells activities. These results demonstrated that Takrisodokyeum extract different results according to the type of tumor cells. And these results also suggested that antitumor effect of Takrisodokyeum might be chiefly due to nonspecific enhancement of NK cell activities and cell-mediated immune responses.