• Environmental Analysis Health and Toxicology
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• 제17권4호
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• pp.325-332
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• 2002

A helper T(Th)1-mediated response is known to enhance cell -mediated immunity, while a Th2-mediated response is associated with the humoral immunity that if elevated IgE levels and eosinophilia. Prostaglandin (PG)E$_2$results in the decreased capability of Iymphocytes to produce Thl cytokines, with a shift toward a Th2 cytokine response. Chlorpyrifos (CPF) has been reported to impair the blastogenesis and response of T Iymphocytes. CPF also induces delayed febrile effects, which results from the activation of COX -PGE$_2$pathway. The purpose of this study is to determine the effort of CPF on the in vitro production of Th cytokines and the role of PGE$_2$on the CPF-induced production of Th cytokines. Splenocytes obtained from male BALB/c mice were pretreated with CPF(0.1, 1, 10 and 100$\mu$M) in the presence of absence of indomethacin or PGE$_2$for 12 h and then were incubated with concanavalin (Con) A for 48 h. These results showed that CPF remarkedly reduced the production of splenic interleukin (IL)-2 and interferon (IFN)-γ in a dose-dependent manner. CPF significantly increased the splenic IL-4 production at low doses (0.1 and 1$\mu$M) but did not affect at high doses (10 and 100 $\mu$M). Indomethacin reduced the CPF-decreased production of IL-2 and IFN-γ in a dose -dependent manner and significantly attenuated the production of IL-4 increased by CPF 0.1 $\mu$M. High dose of CPF significantly reduced the PGE$_2$-decreased production of IL-2 and IFN-γ, while the PGE$_2$- induced production of IL-4 was significantly enhanced by CPF 1 $\mu$M. These findings suggest that CPF nay down-regulate the immune response of Th 1 type by the suppressed production of IL-2 and IFN-γ, with a shift toward a Th2 cytokine response. The CPF-decreased production of Thl cytokines may not be mediated by endogenous PGE$_2$. Also, CPF may attenuate the exogenous PGE$_2$-decreased Th 1 immune response in a dose--dependent manner but may affect dose-independently the PGE$_2$-induced Th2 immune response.

• IMMUNE NETWORK
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• 제8권3호
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• pp.90-97
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• 2008

Background: Hypersensitivity pneumonitis (HP) comprises a group of lung diseases resulting from repeated inhalation of various antigens such as Saccharopolyspora rectivirgula (SR). HP is categorized as a Th1 disease. Therefore, it has been suggested that IL-4, Th2 type cytokine, plays a protective role in the development of HP. However, the functional role of IL-4 in HP has not been extensively investigated in vivo. Therefore, we investigated the functional role of IL-4 in HP using IL-4 knockout (KO) mice. Methods: HP was induced by repeated exposure to SR in C57BL/6 (B6) and IL-4 KO (C57BL/6 background) mice. Results: IL-4 KO mice aggravated HP in terms of histological alteration, SR-specific immune responses, and inflammatory cell infiltration in the lungs compared with B6 mice. IL-4 KO mice produced high levels of IFN-${\gamma}$, TGF-${\beta}$ and TNF-${\alpha}$ in the lungs, whereas B6 mice showed the enhanced production of IL-4. Moreover, chemokines such as MIP-1${\alpha}$, MCP-1, and RANTES were highly expressed in IL-4 KO mice. IFN-${\gamma}$-secreting CD4, CD8 T cells, and neutrophils were enhanced in the bronchoalveolar lavage fluid (BALF) of IL-4 KO mice than those of B6 mice. The administration of recombinant(r) IL-4 restored these immunologic parameters in IL-4 KO mice. Conclusion: These results indicate that IL-4 plays a suppressive role in SR-induced HP by attenuating Th1-dominant immune responses.

• 대한의생명과학회지
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• 제19권2호
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• pp.158-163
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• 2013

Cholestatic liver is associated with hepatic inflammation and elevated proinflammatory cytokines. Recent studies indicate that certain cytokines can modulate bile secretion. In the present study, we have examined the role of interleukin (IL-2) on the bile secretion by a combination of study models. To examine the relevance of IL-2 on bile secretion, the expression of IL-2 and IL-2 receptor (IL-2R) of isolated normal and bile duct ligated (BDL) rats cholangiocytes was first measured by RT-PCR. In BDL rats, the expression of IL-2 and IL-2R was significantly increased compared with normal rats. To study the effect of IL-2 on bile secretion, bile flow was measured in normal and BDL rats. At the level of cholangiocytes, secretory responses of isolated bile duct unit (IBDU)s were quantified by videomicroscopy. The administrations of IL-2 had no significant effect on basal bile secretion in normal and BDL rats. There was no significant effect of IL-2 on basal bile ductular secretion as evidenced by no significant difference in luminal area of the IBDUs perfusedwith 100 pM of IL-2 from those of albumin carrier control. However, the secretin-stimulated bile ductular secretion was significantly (P < 0.01) inhibited by $34{\pm}4%$ (normal, n = 12), $21{\pm}5.3%$ (BDL 2 wk, n = 12) and $15{\pm}5.2%$ (BDL 4 wk, n = 12) with the co-administration of IL-2. As with other cytokines, physiologically relevant concentration of IL-2 can significantly inhibit secretin-stimulated bile ductular secretion. These findings support the important roles of cytokines in modulating bile secretion and may contribute to the cholestasis seen in cholestatic liver diseases.

• Molecular & Cellular Toxicology
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• 제2권4호
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• pp.223-228
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• 2006

Several plant-derived cannabinoids and endogenous ligands for cannabinoid receptors such as 2-arachidonyl-glycerol have been known to inhibit interleukin-2 (IL-2) expression. In the present study, we utilized arachidonylethanolamide (AEA), a putative endogenous ligand for cannabinoid receptors, to determine whether AEA modulated the expression of IL-2. AEA inhibited phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io)-induced IL-2 protein secretion and mRNA expression in EL-4 mouse T-cells as determined by ELISA and RT-PCR, respectively. To further characterize the inhibitory mechanism of AEA at the transcriptional level, we performed promoter study for IL-2 gene in PMA/Io-stimulated EL-4 cells. AEA decreased the transcriptional activity of the nuclear factor of activated T-cells (NF-AT) as well as the IL-2 promoter activity. These results suggest that AEA suppresses IL-2 expression and that the inhibition is mediated, at least in part, through the down-regulation of NF-AT.

• Archives of Pharmacal Research
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• 제21권5호
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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.

• Journal of Ginseng Research
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• 제44권3호
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• pp.453-460
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• 2020

Background: BIOGF1K, a fraction of Panax ginseng, has desirable antimelanogenic, anti-inflammatory, and antiphotoaging properties that could be useful for treating skin conditions. Because its potential positive effects on allergic reactions in skin have not yet been described in detail, this study's main objective was to determine its efficacy in the treatment of atopic dermatitis (AD). Methods: High-performance liquid chromatography was used to verify the compounds in BIOGF1K, and we used the (3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide method to determine its cytotoxicity in RBL-2H3 and HMC-1 cell lines. RBL-2H3 cells were induced using both anti-DNP-IgE/DNP-BSA and calcium ionophore (A2187) treatments, whereas HMC-1 cells were induced using A2187 alone. To measure mast cell degranulation, we performed histamine (enzyme-linked immunosorbent assay) and β-hexosaminidase assays. To quantify interleukin (IL)-4, IL-5, and IL-13 levels in RBL-2H3 cells, we performed quantitative polymerase chain reaction (PCR); to quantify expression levels of IL-4 and IL-13 in HMC-1 cells, we used semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Finally, we detected the total and phosphorylated forms of extracellular signal-regulated kinase, p-38, and c-Jun N-terminal kinase proteins by immunoblotting. Results: BIOGF1K decreased the AD response by reducing both histamine and β-hexosaminidase release as well as reducing the secretion levels of IL-4, IL-5, and IL-13 in RBL-2H3 cells and IL-4 and IL-13 in HMC-1 cells. In addition, BIOGF1K decreased MAPK pathway activation in RBL-2H3 and HMC-1 cells. Conclusions: BIOGF1K attenuated the AD response, hence supporting its use as a promising and natural approach for treating AD.

• 한국약용작물학회지
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• 제18권4호
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• pp.231-237
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• 2010

The present study was conducted to investigate the anti-allergic reaction with Glycyrrhiza uralensis. We examined cell viability, $\beta$-hexosaminidase release, IL-4 and IL-13 mRNA expression from RBL-2H3 cell after pre-treatment with 0, 100, 250, 500, 1000${\mu}g/m{\ell}$ of Glycyrrhiza uralensis water extracts. Effects of Glycyrrhiza uralensis on the degranulation and pro-inflammatory cytokines (IL-4 and IL-13) expression were evaluated with $\beta$-hexosaminidase assay, and RT-PCR analysis. We observed that Glycyrrhiza uralensis concentrations from 100${\mu}g/m{\ell}$ to 1000${\mu}g/m{\ell}$ had no effect on cell survival. The release of $\beta$-hexosaminidase decreased significantly with all concentrations of Glycyrrhiza uralensis extracts. The expression of the IL-4 and IL-13 mRNA were decreased by Glycyrrhiza uralensis in dose-dependent manner. These results that Glycyrrhiza uralensis has an anti-histamin effects and controls IL-4, IL-13 secretion on allergic reaction.

• 한방안이비인후피부과학회지
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• 제23권2호
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• pp.41-56
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• 2010

Objectives : On an experimental basis, the effects of atopic dermatitis induced materials on the expression of cytokine genes in human monocytes (THP-1, U937) and mast cells were studied. This study was carried out to be considered a fundamental knowledge in the research on the good of oriental medicine. Methods : After culturing THP-1, U937, and HMC-1, with the three different concentrations of LPS ($1\;{\mu}g/ml$), DPE ($10\;{\mu}g/ml$), and DNCB ($1\;{\mu}g/ml$), atopic dermatitis induced materials were treated in the culture medium. To investigate cytokine genes expression patterns, with lysis buffer and separation reagent, total RNA was extracted from THP-1, U937, and HMC-1 at intervals of 0, 12, 24, and 48 hours. Both cytokine mRNA expression patterns by atopic dermatitis induced materials and change of cytokine genes expression patterns in relation to atopy by selenium were analyzed with RT-PCR. Also IL-4 and INF-$\gamma$, which were secreted in the HMC-1, were analyzed using ELISA method. Results : 1. After treating THP-1 and U937 with LPS, DPE, and DNCB, there was no significant change in cytokine genes themselves, but various cytokines (IL-4, IL-6, IL-8, IL-13, IFN-$\gamma$, IFN-a, MCP-1, B2-MG) were expressed. 2. In the case of HMC-1, the expressions of IL-6 and IL-8 were significantly increased in the analysis of mRNA expression by dust mite allergens in DPE. 3. As a result of ELISA method, it is certain that IL-4 and IFN-$\gamma$ protein were secreted in the HMC-1 by DPE. 4. Selenium, an essential trace element, decreased the IL-10 and IL-13 expression in the HMC-1 by DPE. Conclusion : The results suggest that it is necessary to choose proper atopic dermatitis induced materials and suitable cultured cells in establishment of in vitro model of atopic dermatitis.

• Childhood Kidney Diseases
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• 제13권2호
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• pp.153-160
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• 2009

목적 : 장점막 손상은 IgA 신증의 병리기전중의 하나로 알려져 있다. 구강항원은 보통 Th2 세포와 비반세포를 활성화 시킨다. 이러한 세포들은 IL-4, IL-5 TGF-${\beta}$와 같은 싸이토카인들을 분비하여 IgA 생성을 증가시킨다. 케토티펜(benzpxycloheptathiophene)은 H1항체이자 비반세포의 막안정제로 IL-4, IL-5, PGE2, LTB4 등의 생산을 억제하고, 질산화산소합성제의 활성화를 감소시켜 위장관막을 보호한다. 저자들은 구강항원으로 인한 IgA 신증의 발병을 케토티펜이 예방할 수 있는지 관찰하였다. 방법 : ICR 생쥐를 이용하여 구강 폴리오백신(백신군)을 투여하면서, 다른 군에서는 케토티펜(케토티펜군)을 백신과 동시에 투여하였다. 결과 : 메산지움의 IgA 침착은 백신군에서 18마리중 11마리에서 발생하였으나, 케토티펜군에서는 9마리 중 3마리에서 볼 수 있었다. 메산지움의 조직 변화는 백신군에서 18마리 중 16마리, 케토티펜 군에서는 9마리 중 5마리에서 볼 수 있었다. 혈청 IL-4, IL-5치는 케토티펜 군에서 백신군과 비교해 다소 낮기는 하지만 의미있는 감소는 하지 않았다. 결론 : 케토티펜은 IgA 신증의 사구체 변화를 감소시키는데 유효한 것으로 사료된다.

• IMMUNE NETWORK
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• 제10권1호
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• pp.1-4
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• 2010

Asthma is characterized by chronic airway inflammation with intense eosinophil and lymphocyte infiltration, mucus hyperproduction, and airway hyperresponsiveness. Accumulating evidence indicates that antigen-specific Th2 cells and their cytokines such as IL-4, IL-5, and IL-13 orchestrate these pathognomonic features of asthma. In addition, we and others have recently shown that IL-17-producing $CD4^+$ T cells (Th17 cells) and IL-23, an IL-12-related cytokine that is essential for survival and functional maturation of Th17 cells, are involved in antigen-induced airway inflammation. In this review, our current understanding of the roles of IL-23 and Th17 cells in the pathogenesis of allergic airway inflammation will be summarized.