• Title, Summary, Keyword: IL-4

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Up-Regulation of Interleukin-4 Receptor Expression by Interleukin-4 and CD40 Ligation via Tyrosine Kinase-Dependent Pathway

  • Kim, Hyun-Il;So, Eui-Young;Yoon, Suk-Ran;Han, Mi-Young;Lee, Choong-Eun
    • BMB Reports
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    • v.31 no.1
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    • pp.83-88
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    • 1998
  • Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4 (IL-4) and CD40 ligation in B cell activation, we have examined the effect of CE40 cross-linking on the IL-4 receptor expression in human B cells using anti-CE40 antibody. We observed that IL-4 and anti-CD40 both induce IL-4 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in a significant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4 action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

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IL-4 Suppresses UVB-induced Apoptosis in Skin

  • Hwang, Ha-Young;Choi, Soo-Young;Kim, Tae-Yoon
    • BMB Reports
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    • v.40 no.1
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    • pp.36-43
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    • 2007
  • In this study, cutaneous role of IL-4 in UVB-induced apoptosis was investigated using transgenic mice with skin-specific expression of IL-4 (IL-4 Tg mice). The transgenic mice did not show any gross clinical abnormalities. However, epidermis was thickened and increased MHC class II positive cells were detected as well as enhanced expression of inflammatory cytokines such as IL-1 and TNF-$\alpha$ in skin. In addition, histological analysis revealed increased infiltration of lymphocytes, acanthosis, hyperkeratosis, and parakeratosis in skin of IL-4 Tg mice. The physiological effect of IL-4 overexpression in skin against environmental stimulus such as UVB was investigated by irradiating wild-type and IL-4 Tg mice with UVB followed by evaluation of apoptosis. The result demonstrated suppressed apoptosis in epidermis of IL-4 Tg mice compared with wild-type mice. To further assess anti-apoptotic function of IL-4 in keratinocytes, stable cell clones were made where IL-4 was constitutively overexpressed and examined for UVB-induced apoptosis. The results showed that apoptosis was remarkably decreased in IL-4 over-expressing cell clones compared with that in mock transfected cells. Collectively, data presented here shows that IL-4 has an inhibitory effect against UVB-induced apoptosis in keratinocytes, suggesting that IL-4 may be an important regulator in cutaneous immunity against UVB.

Effects of Eucalyptus and Geranium on Production of IL-2 and IL-4 in Mouse Splenocytes (Eucalyptus와 geranium이 마우스 splenocytes에서 IL-2 및 IL-4 생성에 대한 효과)

  • Cha Bong Kyu;Chang Myung Woong;Jeong Young Kee;Kim Kwang Hyuk
    • Journal of Life Science
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    • v.16 no.1
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    • pp.162-167
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    • 2006
  • Aromatherpy is the controlled use of essential oils to promote health and well-being. In this work we have investigated the effect of eucalyptus and geranium on the production of interleukin-2 (IL-2) and interleukin4 (IL-4). Mouse splenocytes were incubated with essential oils. The culture supernatants of mouse splenocytes exposed with these oils were harvested to assay IL-2 and IL-4 production. The quantitative changes of IL-2 in splenocytes culture supernatants after exposure with these oils were decreased at high doses, but increased at low doses. But its of IL-4 were increased generally at high doses of eucalyptus. In case of the exposure of geranium, its of IL-4 were dose-dependently increased. These kinds of essential oils showed the probability to improve IL-2- and IL-4-related immune responses at the optimum exposure.

IL-4-deficient Mice Aggravate Hypersensitivity Pneumonitis

  • Hwang, Su-Jin;Chung, Doo-Hyun
    • IMMUNE NETWORK
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    • v.8 no.3
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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.

Difference in the Transcriptional Activity of the Interleukin-4 Promoter Haplotypes (Interleukin-4 유전자의 Promoter 일배체형에 따른 전사능의 차이)

  • Choi, Eun Hwa;Kim, Hee Sup;Chanock, Stephen J.;Lee, Hoan Jong
    • 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.

Immunostimulntory Effects of Immu-Forte at 3 Months Post-Treatment in Mice (면역기능증강성 동암 바이오스 신물질에 대한 3개월간의 마우스 투여후의 면역학적 및 혈액학적 변화)

  • Jung Ji-Youn;Ahn Nam-Shik;Park Joon-Suk;Jo Eun-Hye;Hwang Jae-Woong;Lee Seoung-Hun;Park Jung-Ran;Kim Sun-Jung;Lee Yong-Geon;Jeong Yun-Hyeok;Chung Ji-Hye;Lee Soo-Jin;Lee Sang-Bum
    • Journal of Food Hygiene and Safety
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    • v.20 no.2
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    • pp.118-122
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    • 2005
  • Immu-Forte (Dong-Ahm Bio's. Corp., Korea) was evaluated fir its effectiveness as a nonspecific immunostimulator in mice. The effects of Immu-Forte were determined by analysis of cytokines using ELISh and phenotype of leukocyte subpopulations using monoclonal antibodies specific to mouse leukocyte differentiation antigens and flow cytometry. CD4 T cells, CD8 T cells, macrophages, IL-12 and IFN-r in Immu-Forte EX-treated middle dose group increased in 3 months posttreatment and were significantly higher (p<0.05) than that of control at 3 months posttreatment. All T cells, all B cells, macrophages, IL-2, IL-4 and IL-12 in Immu-Forte EX-treated low dose uoup increased in 3 months posttreatment and were significantly higher (p<0.05) than that of control at 3 months posttreatment. In the Immu-Forte soy-treated group, CD4 T cells, IL-2, IL-4 and IL-12 were significantly higher in high dose-treated group, and CD 4 T cell, macrophages, IL-2, IL-4 and IL-12 were significantly higher in middle dose-treated group, and all T cell, IL-2, IL-4 and IL-12 were significantly higher in low dose-treated group. In the Itnmu-Forte A-treated group, macrophages, m cells and IL-12 in high dose-treated group and all T cells, macrophages, NK cells, IL-2, IL-4 and IL-12 in middle dose-treated group and NK cells in low dose-treated group were significantly higher (p<0.05) than that of control at 3 months posttreatment. In the Immu-Forte F-treated Group, all B cells, IL-4 and IL-12 in high dose-treated group and all T cells, aBl B cells, CD 4 T cells, CD8 T cells, macrophage, IL-2, IL-4, IL-12 and IFN-r in middle dose-treated group and NK cells and IL-12 in low dose-treated group were significantly higher (p<0.05) than that of control at 3 months posttreatment. In conclusion, the study has demonstrated that Immu-Forte had an immunostimulatory effect on mice through proliferation and activation of mouse immune cells.

Changes of immunostimulatory effects by Immu-Forte on mice (면역기능 증강 신물질에 대한 마우스의 면역학적 및 혈액학적 변화)

  • Jung, Ji-Youn
    • Korean Journal of Veterinary Research
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    • v.45 no.4
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    • pp.501-505
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    • 2005
  • Immu-Forte composed of chitosan, ${\beta}-glucan$, manno-oligosaccharide and pangamic acid was evaluated for its effectiveness as a nonspecific immunostimulator in mice. The effects of Immu-Forte were determined by analysis of cytokines using ELISA and phenotype of leukocyte subpopulations using monoclonal antibodies specific to mouse leukocyte differentiation antigens and flow cytometry. All T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, IL-2, IL-4, IL-12 and IFN-r in Immu-Forte A-treated group increased in 1 months posttreatment and were significantly higher (p < 0.05) than that of control at 1 months posttreatment. All T cells, all B cells, CD4 T cells, CD8 T cells, macrophages and IL-2 in Immu-Forte EX-treated low and middle dose groups increased in 1 months posttreatment and were significantly higher (p < 0.05) than that of control at 1 months posttreatment. In the Immu-Forte soybean-treated group, NK cells and IL-4 were significantly higher in middle dose-treated group, and IL-2, IL-4 and IFN-r were significantly higher in low dose-treated group. In the Immu-Forte F-treated group, all T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, NK cells, IL-2, IL-4, IL-12 and IFN-r in high dose-treated group and all T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, IL-2, IL-4, IL-12 and IFN-r in middle dose-treated group and NK cells, IL-2, IL-4, IL-12 and IFN-r in low dose-treated group were significantly higher (p < 0.05) than that of control at 1 months posttreatment. In conclusion, this study has demonstrated that Immu-Forte had an immunostimulatory effect on mice through proliferation and activation of mouse immune cells.

Effects of Chitosan on the Production of Th1 and Th2 Cytokines in Mice (키토산이 Th1과 Th2 사이토카인 생성에 미치는 효과)

  • Kim, Kwang-Hyuk
    • Journal of Life Science
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    • v.19 no.3
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    • pp.411-416
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    • 2009
  • Chitosan is derived from chitin by a process of controlled deacetylation. In the present study, we investigated the effects of chitosan on the production of cytokines such as interleukin-2 (IL-2), interferon-$\gamma$ (IFN-$\gamma$), interleukin-4 (IL-4), and interleukin-10 (IL-10) in mice. The culture supernatants of splenocytes exposed with chitosan alone or chitosan plus cell stimulants, lipopolysaccharide (LPS), concanavalin A (Con A), and phytohemagglutinin-P (PHA-P) were harvested to assay IL-2, IFN-$\gamma$, IL-4, and IL-10 production. IL-2, IFN-$\gamma$, and IL-4 from splenocytes exposed to chitosan showed a greater increase compared to the PBS control group. IL-2 and IFN-$\gamma$ levels in the culture supernatants from splenocytes exposed to LPS+chitosan were higher than those of the groups exposed to LPS alone. IL-4 and IL-10 levels in the culture supernatants from splenocytes exposed to LPS+chitosan were lower than those of the groups exposed to LPS only. These findings demonstrate that chitosan upregulates the immune responses by Th1 cytokines (IL-2 and IFN-$\gamma$) and downregulates those by Th2 cytokines (IL-4 and IL-10) in LPS-associated immunity. These results show the potential of its usefulness for balancing the Th1/Th2 immune response, if more research results were accumulated.

Effects of Kamichihyo-san on Anti-CD40 and Recombinant Interleukin-4 Induced Cytokine Production and Immunoglobulin E in Highly Purified Mouse B Cells (생쥐의 B 세포에서 anti-CD40과 rIL-4로 유도된 사이토카인 생산과 면역글로블린 E에 대한 가미치효산의 효과)

  • Ham Chul in;Park Yang chun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.6
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    • pp.1479-1486
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    • 2003
  • In order to evaluate the antiallergic effects of Kamiohihyosan(KCHS), studies were done. We measured the cytotoxic activity for lung fibroblast cell, cytokines transcript expression, production of IL-4, IL-10, IFN-γ, proliferation of B cell in anti-CD40mAb plus rIL-4 stimulated murine splenic B cells. The results were obtained as follows: KCHS was not showed cytotoxicity in the fibroblast lung cell, KCHS increased the gene synthesis of INF-γ, TNF-α, IL1-β, IL-6, IL-10(m-RNA), KCHS decreased the gene synthesis of IL-4, IL-5, TGF-β(m-RNA), KCHS decreased the appearance of IL-4, IgE significantly, KCHS increased the appearance of IL-10, IFN-γ significantly, KCHS decreased the proliferation of B cell significantly, The facts above prove that KCHS is effective against the allergy. Thus, I think that we should study on this continuously.

Genetic Variants of IL-13 and IL-4 in the Korean Population: Polymorphisms, Haplotypes and Linkage Disequilibrium

  • Ryu, Ha-Jung;Jung, Ho-Youl;Park, Jung-Sun;Kim, Jun-Woo;Kim, Hyung-Tae;Park, Choon-Sik;Han, Bok-Ghee;Koh, In-Song;Park, Chan;Kimm, Ku-Chan;Oh, Berm-Seok;Lee, Jong-Keuk
    • Genomics & Informatics
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    • v.3 no.4
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    • pp.149-153
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    • 2005
  • Asthma is an inflammatory airways disease characterized by bronchial hyperresponsiveness and airways obstruction, which results from a complex interaction of genetic and environmental factors. Interleukin (IL)-13 and IL-4 are important in IgE synthesis and allergic inflammation, therefore genes encoding IL-13 and IL-4 are candidates for predisposition to asthma. In the present study, we screened single-nucleotide polymorphisms (SNPs) in IL-13 and IL-4 and examined whether they are risk factors for asthma. We resequenced all exons and the promoter region in 12 asthma patients and 12 normal controls, and identified 18 SNPs including 2 novel SNPs. The linkage disequilibrium(LD) pattern was evaluated with 16 common SNPs, and haplotypes were also estimated within the block. Although IL-13 and IL-4 are localized within 27 kb on chromosome 5q31 and share many biological profiles, this region was partitioned into 2 blocks. One SNP and three SNPs were determined as haplotype-taggingSNPs (htSNPs) within IL-13 and IL-4 haplotype-block, respectively. No significant associations were observed between any of the SNPs or haplotypes and development of asthma in small number of Korean subjects. However, the genetic variants of IL-13 and IL-4 would provide valuable strategies for the genotyping studies in large population.