• Archives of Pharmacal Research
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• v.21 no.5
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• pp.537-542
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• 1998

to more effectively drive immune responses toward antigen-specific T helper type 2 (Th2) cell-mediated responses, we constructed a mammalian expression vetor (oPVA/IL4) carrying a fused gene in which the ovalbumin (OVA) cDNA was covalently linked to murine interleukin-4 (IL-4) cDNA. A biologically active OVA/IL4 DNA, as demonstrated by Wes tern blotting and cytokine bioassay. In tramuscular injection of BALB/c mice with the pOVA/IL4 DNA increased both the production of OVA-specific IL-4 by CD$4^{+}$ T cells and the ratio of anti-OVA lgG1 to anti-OVA lgG2a isotypes, while the injection with the pOVA DNA alone, or with the mixture of the pOVA and pIL4 DNA did no or little increase. furthermore, the OVA-specific, Th2 cell-mediated immune responses were significantly enhanced by multiple injections with the pOVA/IL4 DNA. These studies indicate that the direct linkage of an OVA gene to an IL-4 gene in the expression plasmid confines the effects of IL-4 to the OVA-specific cells, efficiently driving the immune response toward OVA-specific, Th2 cell-mediated responses.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.42.1-42.20
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• 2021

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.1-10
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• 2005

Background: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-${\alpha}$ or lamivudine. However, interferon-${\alpha}$ is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. Methods: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb / c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. Results: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. Conclusion: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.

• Parasites, Hosts and Diseases
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• v.53 no.4
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• pp.431-438
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• 2015

In Trichinella spiralis infection, type 2 helper T (Th2) cell-related and regulatory T ($T_{reg}$) cell-related immune responses are the most important immune events. In order to clarify which Toll-like receptors (TLRs) are closely associated with these responses, we analyzed the expression of mouse TLR genes in the small intestine and muscle tissue during T. spiralis infection. In addition, the expression of several chemokine- and cytokine-encoding genes, which are related to Th2 and $T_{reg}$ cell mediated immune responses, were analyzed in mouse embryonic fibroblasts (MEFs) isolated from myeloid differentiation factor 88 (MyD88)/TIR-associated proteins (TIRAP) and Toll receptor-associated activator of interferons (TRIF) adapter protein deficient and wild type (WT) mice. The results showed significantly increased TLR4 and TLR9 gene expression in the small intestine after 2 weeks of T. spiralis infection. In the muscle, TLR1, TLR2, TLR5, and TLR9 gene expression significantly increased after 4 weeks of infection. Only the expression of the TLR4 and TLR9 genes was significantly elevated in WT MEF cells after treatment with excretory-secretory (ES) proteins. Gene expression for Th2 chemokine genes were highly enhanced by ES proteins in WT MEF cells, while this elevation was slightly reduced in MyD88/$TIRAP^{-/-}$ MEF cells, and quite substantially decreased in $TRIF^{-/-}$ MEF cells. In contrast, IL-10 and $TGF-{\beta}$ expression levels were not elevated in MyD88/$TIRAP^{-/-}$ MEF cells. In conclusion, we suggest that TLR4 and TLR9 might be closely linked to Th2 cell and $T_{reg}$ cell mediated immune responses, although additional data are needed to convincingly prove this observation.

• Journal of Life Science
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• v.22 no.3
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• pp.298-305
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• 2012

The general term flavonoids is often used to categorize a family of natural compounds that are highly abundant in all higher plants, and which in recent years have attracted scientific interest as therapeutics. Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. It is found in green vegetables such as spinach and kale, and has been demonstrated to exert anti-inflammatory activities. However, its anti-allergic effect in the Th1/Th2 immune response is poorly understood. In this study, we attempt to determine whether lutein regulates inflammatory mediators in an ovalbumin (OVA)-induced murine asthma model. To address this, mice were sensitized and challenged with OVA, and then treated with lutein before the last OVA challenge. Administration of lutein significantly suppressed the OVA-induced airway hyper-responsiveness. It also resulted in a significant alleviation of the infiltration of inflammatory cells into the bronchoalveolar lavage. Additionally, lutein attenuated the increased expression of Th2 responses in OVA-challenged mice. These results demonstrate that lutein is a potent inhibitor that reduces Th2 immune responses. Furthermore, they show that the immunopharmacological function is mediated by a pathway that involves and is regulated by Th2 immune response.

• The Korea Journal of Herbology
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• v.23 no.2
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• pp.51-58
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• 2008

Objectives : Trimellitic anhydride (TMA), a sensitizer that induces occupational asthma and atopic dermatitis, is widely used industrially to make epoxy and alkyd resins, plasticizers, high temperature polymer, and surfactants. The aim of this study was to investigative the effects of aqueous extracts of Lonicera japonica Flower(LJFAE) on TMA-induced contact hypersensitivity (CHS) in Balb/c mice. Methods : The dried flowers of L. japonica were extracted with distilled water at $100^{\circ}C$ for 7 h. The extract was freeze-dried following filteration through 0.45 ${\mu}m$ filter. Mice were orally administrated with or without LJFE of a different doses(25-100 mg/kg) for 28 days. In the challenge period, mice were externally applied at difference doses of LJFAE one time per day 30 min before TMA treatment. We examined the effects of LJFAE on the the serum levels of IgE and prostagladin E2 (PGE2), the Thl/Th2 cytokine production of spleen cells, ear swelling responses, and the leukocyte infiltration induced by TMA. Results : The orally and externally administration of LJFAE dose-dependently reduced the serum levels of IgE and PGE2 production as well as ear swelling responses and leukocyte infiltration in TMA-induced Balb/c mice. Furthermore, the levels of Thl (TNF-${\alpha}$, IFN-${\gammer}$, IL-2)/Th2 (IL-4, IL-5, IL-13) cytokine production from spleen cells stimulated with anti-CD3 and CD28 mAbs was markedly suppressed by the orally and externally treatment with LJFAE in a concentration dependent manner. Conclusions : These results suggest that LJFAE suppresses the inflammatory mediators and regulates the Thl/Th2 cytokines. Therefore, these properties may contribute to the strong anti-CHS response effect of LJFAE.

• YAKHAK HOEJI
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• v.52 no.1
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• pp.27-32
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• 2008

Water extracts of Acanthopanax divaricatus var. albeofructus (ADA) fruits were used to treat hPBMC to determine the mechanisms for the immunomodulatory effects. The secretion level of various cytokines including Th-1 type (IL-2, L-12, $IFN-{\gamma}$ and $TNF-{\alpha}$) and Th-2 type (IL-6, IL-8 and IL-10) were measured using ELISA. A significant increase of Th-1 type cytokine secretion was observed in the presence of extract while Th-2 cytokine, IL-6 was suppressed. Our results suggest that ADA fruit extract may influence the anticancer immune responses towards a predominance of Th-1 cytokines in the immune system.

• Nutrition Research and Practice
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• v.17 no.2
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• pp.356-370
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• 2023

BACKGROUND/OBJECTIVES: School food service has played an important role in promoting the health and physical condition of students by providing students with a balanced and nutritious diet. Therefore, boosting the quality of school food service and improving the students' satisfaction is critical. For this purpose, this study examined the structural causal relationship among the quality of school food service factors, emotional responses, and satisfaction in China. SUBJECTS/METHODS: This study was conducted with 4th-6th-grade students from 6 junior high schools in Henan province of China, with 590 questionnaire responses (87.3%) collected and statistically analyzed. RESULTS: The school food service quality factors (including menu management, dietary education, facilities management, price and food distribution management, and personal hygiene during meals) must be enhanced to boost the students' satisfaction. In addition, the study used questionnaire survey data to validate the full mediation of students' emotional responses between school food service quality factors and student satisfaction. CONCLUSIONS: Students' emotions also play an important role in influencing the quality of school food service, all of which affect the emotional responses of students. Therefore, students' positive emotions are an important indicator for improving the quality of school food service. A national support policy is necessary for the ongoing maintenance and development of various programs that drive students' satisfaction and promote the adoption of education guidelines for school food service in China.

• Parasites, Hosts and Diseases
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• v.44 no.3
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• pp.209-219
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• 2006

Toxoplasma gondii has been shown to result in life-threatening encephalitis in immunocompromised patients after reactivation of dormant parasites. In order to obtain information on immune responses related to this phenomenon, BALB/c mice were infected with 25 cysts of the 76K strain of T. gondii, then, treated orally with dexamethasone (Toxo/Dexa-treated group) in order to reactivate the chronic toxoplasmosis. None of the T. gondii-infected mice died during the experimental periods, whereas the Toxo/Dexa-treated mice evidenced a significant attenuation of survival periods. Toxoplasma-specific IgG2a, IgA and IgM titers in sera were significantly depressed in the Toxo/Dexa-treated mice; however, the IgG1 sera titers were similar to those seen in the Toxoplasma-infected mice. The percentages of CD4+ and $CD8\alpha+$ T cells in the Toxo/Dexa-treated mice were significantly reduced 2 weeks after dexamethasone treatment. $IFN-\gamma$ and IL-10 production levels in the Toxo/Dexa-treated mice were depressed significantly, whereas IL-4 production was increased temporarily. The expression levels of the Toxoplasma-specific P30 and B1 genes were found to have been increased in the Toxo/Dexa-treated mice in comparison with the Toxoplasma-infected mice. Collectively, the findings of this study demonstrate that reactivation of murine toxoplasmosis as the result of dexamethasone treatment induced a depression in Th1 immune responses, whereas Th2 immune responses were not significantly influenced.

• The Korea Journal of Herbology
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• v.28 no.2
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• pp.9-15
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• 2013

Objectives : The root of Codonopsis pilosula (Fr.) Nannf. (Codonopsis Pilosulae Radix) has been traditionally used as a oriental medicine with an anti-thrombotic, antidiabetic, anticancer, and anti-gastric ulcer effects and immunological adjuvant. In this study, we investigated the effect of 70% ethanol extract of Codonopsis Pilosulae Radix (CPR-E) on ovalbumin (OVA)-induced allergic responses in mice. Methods : Mice were sensitized (1, 8, and 15 days) with OVA and airway challenged(22, 24, 26, 28, and 30 days) to induced allergic responses. CPR-E extract at doses of 50 and 100 mg/kg/body weight was orally administered from days 21 to 30 consecutively. The levels of allergic mediators such as histamine, OVA-specific immunoglobulin (Ig) E, and Th1/Th2 cytokines such as IFN-${\gamma}$ and IL-4 were measured in the sera of mice by ELISA. The histological change of lung tissue was observed by hematoxylin and eosin (H&E) staining. Results : CPR-E extract significantly decreased the serum levels of histamine, OVA-specific IgE, and IL-4 compared with those of OVA control group, but significantly increased the serum level of IFN-${\gamma}$. Based on H&E staining, CPR-E extract inhibited the infiltration of inflammatory cells into lung tissues with histological changes. Conclusions : These results indicate that CPR-E extract has anti-inflammatory and anti-allergic responses through regulating the cytokine balance, suggesting that the extract may be useful for the treatment of allergic inflammatory diseases such as bronchial asthma and allergic rhinitis.