• Journal of Microbiology and Biotechnology
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• v.20 no.11
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• pp.1585-1591
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• 2010

A comprehensive study on the production of inflammatory mediators in the lungs of BALB/c mice following infection with Stenotrophomonas maltophilia was conducted. The levels of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-${\alpha}$), and interleukin-1${\beta}$ (IL-1${\beta}$) were raised in the lungs of infected mice compared with control. The production of anti-inflammatory cytokine IL-10 was slightly delayed. Its peak level was on the $2^{nd}$ day, whereas the peak of pro-inflammatory cytokines was observed on day 1 after intranasal challenge. This was accompanied by a rise in myeloperoxidase (MPO) and malondialdehyde (MDA) on day 1. The increase in MPO levels matched with histopathological observations, as neutrophils infiltration was detected on the first day. Alveolar macrophages (AMs) obtained from infected animals showed a higher rate of uptake and killing when exposed to bacteria in vitro, compared with similar experiments conducted with AMs from normal mice (control). This suggests that AMs were more efficient in cleaning the bacteria. The nitric oxide (NO) production however started early during infection but reached its maximum on the $3^{rd}$ day. No mortality was observed among the infected animals, and infection was resolved by the $5^{th}$ day post infection. No drastic changes in the lung tissue were observed on histopathological examination.

• Parasites, Hosts and Diseases
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• v.40 no.4
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• pp.165-172
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• 2002

Collaborative studies have identified some genetic factors contributing to the development of severe forms of malaria and schistosomiasis. In Thailand, the $TNF-{\alpha}{\;}5'-flanking$ region shows biallelic polymorphic sites at nucleotides -238, -308, -857, -863, and -1031, and seven alleles have been identified in patients from Myanmar. We found that the TNF promoter (TNFP)-D allele was significantly associated with cerebral malaria in populations from Karen (P < 0.0001. OR ＝ 124.86) and ethnic Burma (P < 0.0001, OR = 34.50) . In China, we have identified two major genes related to the severity of liver fibrosis, one an HLA class II gene, and the other the IL-13 gene. The frequency of the HLA- DRB5*0101 allele and that of the IL-13 promoter A/A (IL- l3P- A/A) genotype were elevated in fibrotic patients, although the two genes are located on different chromosomes, chromosomes 6p and 5q, respectively Subjects with both genotypes had odds ratios (OR = 24.5) much higher than the sum of the ratios for each individual genotype (OR ＝ 5.1,95% Confidence Interval 1.3-24.7 for HLA-DRB5*0101, OR ＝ 3.1 95% CI 1.5 - 6.5 for IL-l3P-A/A). That the effects of the two susceptibility markers are synergistic rather than additive, strongly suggests that the pathogenic Th2 response directly influences the prognosis of post-schistosomal liver fibrosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.1017-1024
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• 2007

Thymus and activation-regulated chemokine (TARC/CCL-17), produced by keratinocytes, is a CC chemokine known to selectively Th2 type T cells via $CCR4^+$ and is implicated in the development of atopic dermatitis (AD). TARC/CCL17 expression was induced by cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). We recently found that the wogonin, a flavone isolated from Scutellaria baicalensis, suppressed TARC expression via heme oxygenase 1 (HO1) in human keratinocytes induced with mite antigen. However, little is known about the inhibitory mechanism of wogonin on TARC/CCL-17 expression stimulated with cytokines. To investigate the inhibitory mechanism, I determined the inhibitory effects of wogonin on the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and $I{\kappa}B{\alpha}$ phosphorylation, and also examined the activation of p38 MAP kainase in HaCaT keratinocytes stimulated with TNF-${\alpha}$ and IFN-${\gamma}$. Wogonin inhibited NF-${\kappa}B$-DNA complex, NF-${\kappa}B$ binding activity, and the phosphorylation of $I{\kappa}B{\alpha}$ in a dose dependent manner. Wogonin also inhibited the translocation of NF-${\kappa}B$ from cytosol to nucleus. Moreover, the phosphorylation of of p38 MAP kinase in the TNF-${\alpha}$ and IFN-${\gamma}$-stimulated HaCaT keratinocytes were suppressed by wogonin in a dose dependent manner. These results suggest that wogonin may inhibit cytokine-induced NF-${\kappa}B$ activation by $I{\kappa}B{\alpha}$ degradation via suppression of p38 MAP kinase signaling pathway in keratinocytes and modulation of wogonin signaling pathway may be beneficial for the treatment of AD.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5225-5230
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• 2013

Background: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. Materials and Methods: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. Results: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera ($0.29{\pm}0.54$, $0.03{\pm}0.15$ and $0.16{\pm}0.68$ vs. $0.00{\pm}0.00pg/ml$; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls ($2.34{\pm}4.35$ vs. $4.67{\pm}4.32pg/ml$; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. Conclusions: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases.

• Parasites, Hosts and Diseases
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• v.38 no.2
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• pp.85-90
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• 2000

To assess the relationship between the changes of cellular components and the production of Th 1 cytokine in the immune tissue, inbred C57BL/6 mice were orally infected with 40 cysts of 76K strain of Toxoplosma gondii. The sequential change of cell differentials and $IFN-{\gamma}$ production of splenocytes were analyzed by Diff-Quik stain and RT-PCR. There were no significant proportional changes of cellular components of splenocytes until day 4 postinfection (Pl) as compared to those of day 0, and the relative percentage of macrophages and neutrophils/eosinophils increased significantly (p<0.01) thereafter. The expression of $IFN-{\gamma}$ mRNA of $CD3^{-}$ cells was observed from day 1 Pl at a low level. However, $IFN-{\gamma}$ production of $CD3^{+}$ cells increased significantly from day 4 Pl (p<0.01) which progressively increased thereafter. These findings provide the relative percentages of granulocytes and macrophages were increased in conjunction with increase of total number of splenocytes after oral infection with T. gondii in the susceptible murine hosts, and lymphocytes were the major cellular components and the important source of $IFN-{\gamma}$.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.8
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• pp.1121-1127
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• 2015

This study investigated the effects of Myagropsis myagroides ethanol extract (MMEE) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in BALB/c mice. The effects of MMEE on DNCB-induced BALB/c mice were evaluated by examining skin symptom severity, levels of total immunoglobulin E (IgE), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin (IL)-4, and IL-10 in serum, and levels of IL-4, IL-5, IL-13, and $interferon-{\gamma}$ ($IFN-{\gamma}$) in splenocytes. MMEE significantly reduced the total clinical severity score, total IgE levels, as well as $TNF-{\alpha}$ and IL-4 production in an AD mouse model but increased IL-10 production. Production of IL-4, IL-5, and IL-13 in splenocytes was reduced by MMEE, whereas $IFN-{\gamma}$ production increased. These results suggest that MMEE can inhibit the development of AD-like skin lesions in BALB/c mice by modulating the immune response and may be an effective potential therapeutic agent for AD.

• Journal of the korean veterinary medical association
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• v.32 no.1
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• pp.43-51
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• 1996

경구적으로 투여된 항원에 대해서 특이적으로 T세포의 기능과 항체산생이 억제되는 현상이 경구면역관용(oral tolerance)인 것이다. 지금까지 해석이 곤란하였던 이 현상에 대해서 최근 분자생물학적인 기법이 적용되기 시작한 결과, 이 현상에 관여하는 세포가 주로 $CD8^+$ T세포에의한 억제 혹은 $CD4^+$T세포의 불응답(unresponsiveness)에 기인하다는 것이 명백해졌다. 또한 각종 cytokine중 IFN$\gamma$, TGF$\beta$, IL-10 등이 이 현상에 있어 중요한 역할을 담당한다는 것이 밝혀지고 있다. 사실 경구면역관용은 말초면역관용을 야기한다는 것이 오래전부터 알려진 한 방도이다. 경구적으로 투여된 항원이 관용을 야기하는 일차적인 기전은 능동적인 억제의 발생 혹은 clone성 anergy(과민증에 대한 무감증)에 의거하는 것이다. 낮은 량의 경구투여항원은 능동적인 억제를 야기하기 쉬우나 반대로 높은 양의 경구투여항원은 clone성 anergy를 야기하는 경향이 있다. 능동적인 억제를 매개하는 조절세포는 경구면역관용에 의해서 격발된 후 TGF$\beta$및 IL-4와 같은 억제성 cytokine의 분비에 의해서 능동적 억제작용을 한다. 더구나 GALT(gut-associated lymphoid tissue)를 선별적으로 자극하는 항원은 Th2형 세포반응을 발생한다. 또한 이와같은 유도기구의 해석과 동시에 사람에서 면역반응의 이상으로 야기되는 관절 rheumatism이나 다발성경화증(multiple sclerosis) 그리고 각종 allergy도 이 경구면역관용을 이용하여 치료하는 것이 가능하게 되었다는 것이다.

• Korean Journal of Food Science and Technology
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• v.40 no.5
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• pp.574-579
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• 2008

Propolis is the generic term for the resinous substance collected by honey bees from a variety of plant sources. In this study, we have assessed the immunomodulatory properties of propolis (P) and fermented-propolis (FP) in BALB/c mice. Mice were subjected to gavage once a day (for 14 days) with 50, 100, 200 mg/kg body weight P, FP, or vehicle. Lymphocytes were isolated from the spleen and mesenteric lymph nodes (MLN) and the immune cell proportions, proliferative activities, and cytokine production were evaluated. The P- and FP-administration induced similar, but differential, alterations in the percentage of immune cell populations and their biological functions, including cytokine production and NK cell cytotoxicity. The proportion of$ CD4^+$ and $CD8^+$ T cells in the spleen was increased slightly in the P- and FP-administered mice as compared to the vehicle-treated mice. In MLN, the percentage of $CD4^+$ T cells was increased significantly in the 200 mg/kg P-treated mice. The mice which were treated with P and FP evidenced significantly increased interferon-$\gamma$ and interleukin-4 production in concanavalin A-stimulated splenocytes, whereas the production of theses cytokines was not shown to be induced by P-treatment. In addition, NK cell activity was also increased dramatically by the administration of P and FP. Collectively, these findings showed that P and FP are wide-spectrum immunomodulators, which may modulate both innate and adaptive immune responses.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.258-264
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• 2002

Zinc plays an important role in immunobiological responses, while excessive zinc attenuates immune functions in a dose-dependent manner. Zinc excess has been reported to increase levels of plasma prostaglandin E$_2$ (PGE$_2$), which is known to inhibit production of Th (helper T) 1-associated cytokines and to induce inflammatory responses. Thus, this study was investigated the effects of indomethacin, a potent inhibitor of PGE$_2$ synthesis, on the proinflammatory cytokine and lymphokine production in ICR mice exposed to excessive zinc. Indomethacin at doses of 5 mg/kg was administered i.p. 30 minutes before zinc chloride (Zn) 30 mg/kg orally daily for 10 days. Excessive Zn remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$ levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the excessive Zn-induced levels of IL-1$\beta$. In serum, excessive Zn significantly decreased the levels of IL-2 and interferon (IFN)-${\gamma}$ compared with those in controls, whereas indomethacin significantly enhanced the excessive Zn-decreased levels of IFN-${\gamma}$ but did not affect the Zn-decreased levels of serum IL-2. In splenic supernatants, All of excessive Zn, indomethacin, and combination of Zn and indomethacin significantly enhanced IL-2 levels compared with those in controls, but indomethacin didn't affect the Zn-induced production of IL-2. These data, therefore, suggest that indomethacin significantly attenuated the in vivo and ex vivo IL-1$\beta$ production increased by excessive zinc and remarkedly enhanced the in vivo excessive zinc-suppressed production of IFN-${\gamma}$ but not IL-2.

• Clinical and Experimental Pediatrics
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• v.48 no.5
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• pp.495-499
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• 2005

Purpose : Interleukin-4(IL-4) is a critical component of the Th2 cytokine pathway and contributes to severity of respiratory syncytial virus(RSV) bronchiolitis. Previous studies observed an association between severe RSV bronchiolitis in Korean children with a common haplotype of the IL4 promoter. This study was performed to investigate functional differences of the variant IL4 promoter haplotypes. Methods : Genomic DNA was obtained from 20 children from 6 to 48 months of age in the Department of Pediatrics, Seoul National University Bundang Hospital. The IL4 promoter spanning an 1.2 kb region was amplified and haplotype was determined by cloning and the PHASE reconstruction. Transcriptional activity of Jurkat T cells which were transfected with each IL4 haplotype were analyzed by use of luciferase assay. Results : Three haplotypes of the IL4 promoter have been identified with the frequency of GCC(7 percent), TCC(17 percent), and TTT(76 percent). The TTT haplotype demonstrated the highest luciferase values in both unstimulated and PMA-stimulated Jurkat T cells. Increases in transcriptional activity compared to GCC have been shown in TTT(5.3 fold higher) followed by TCC(4.2 fold higher) in unstimulated Jurkat T cells. Conclusion : We provided evidence that increased transcriptional activity of the TTT haplotype of the IL4 promoter, which has previously been over-represented in Korean children with severe RSV bronchiolitis. Therefore, IL-4 could play a potential role in the pathogenesis of RSV infection, possibly via an altered transcriptional activity of the different IL4 haplotypes.