본문 바로가기
KERD
논문KCI 등재

1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) Modulates Th2 Immunity through Attenuation of IL-4 Expression

2

조회

0

다운로드

2

인용

0

참고문헌

키워드

초록

Controlling balance between T-helper type 1 (Th1) and T-helper type 2 (Th2) plays a pivotal role in maintaining the biological rhythm of Th1/Th2 and circumventing diseases caused by Th1/Th2 imbalance. Interleukin 4 (IL-4) is a Th2-type cytokine and often associated with hypersensitivity- related diseases such as atopic dermatitis and allergies when overexpressed. In this study, we have tried to elucidate the function of 1-palmitoyl-2-linoleoyl-3-acetyl- rac-glycerol (EC-18) as an essential modulator of Th1/ Th2 balance. EC-18 has showed an inhibitory effect on the production of IL-4 in a dose-dependent manner. RT-PCR analysis has proved EC-18 affect the transcription of IL-4. By analyzing the phosphorylation status of Signal transducer and activator of transcription 6 (STAT6), which is a transcriptional activator of IL-4 expression, we discovered that EC-18 induced the decrease of STAT6 activity in several stimulated cell lines, which was also showed in STAT6 reporter analysis. Co-treatment of EC-18 significantly weakened atopy-like phenotypes in mice treated with an allergen. Collectively, our results suggest that EC-18 is a potent Th2 modulating factor by regulating the transcription of IL-4 via STAT6 modulation, and could be developed for immune-modulatory therapeutics.

Abstract

Controlling balance between T-helper type 1 (Th1) and T-helper type 2 (Th2) plays a pivotal role in maintaining the biological rhythm of Th1/Th2 and circumventing diseases caused by Th1/Th2 imbalance. Interleukin 4 (IL-4) is a Th2-type cytokine and often associated with hypersensitivity- related diseases such as atopic dermatitis and allergies when overexpressed. In this study, we have tried to elucidate the function of 1-palmitoyl-2-linoleoyl-3-acetyl- rac-glycerol (EC-18) as an essential modulator of Th1/ Th2 balance. EC-18 has showed an inhibitory effect on the production of IL-4 in a dose-dependent manner. RT-PCR analysis has proved EC-18 affect the transcription of IL-4. By analyzing the phosphorylation status of Signal transducer and activator of transcription 6 (STAT6), which is a transcriptional activator of IL-4 expression, we discovered that EC-18 induced the decrease of STAT6 activity in several stimulated cell lines, which was also showed in STAT6 reporter analysis. Co-treatment of EC-18 significantly weakened atopy-like phenotypes in mice treated with an allergen. Collectively, our results suggest that EC-18 is a potent Th2 modulating factor by regulating the transcription of IL-4 via STAT6 modulation, and could be developed for immune-modulatory therapeutics.

참고문헌 (39)

  1. Kleiman, R., "Optically active aceto-triglycerides of oil from Euonymus verrucosus seed", Lipids, 1, pp.286~287 (1966)
  2. Myher, J. J., "Identification of the more complex triacylglycerols in bovine milk fat by gas chromatography-mass spectrometry using polar capillary columns", J. Chromatogr, 452, pp.93~118 (1988)
  3. Limb, J. K., "Isolation characterization of monoacetyldiglycerides from bovine udder", J. Lipid Res, 40, pp.2169~2176 (1999)
  4. Yang, H. O., "Purification structural determination of hematopoietic stem cell-stimulating monoacetyldiglycerides from Cervus nippon (deer antler)", Chem. Pharm. Bull, 52, pp.874~878 (2004)
  5. Lee, T. S., "Preparation of glycerol derivatives intermediates therefor.", KR 10-0789323, ~ (2005)
  6. Lee, T. S., "Preparation method of 1-palmitoyl-3-acetylglycerol, preparation method of 1-palmitoyl-2-linoleoyl-3-acetylglycerol using same.", WO 2013, 2013
  7. Yang, H. O., "Stimulatory effects of monoacetyldiglycerides on hematopoiesis", Biol. Pharm. Bull, 27, pp.1121~1125 (2004)
  8. 김명환, "EC-18, a Synthetic Monoacetyldiacylglyceride, Inhibits Hematogenous Metastasis of KIGB-5 Biliary Cancer Cell in Hamster Model", Journal of Korean Medical Science, 24(3), pp.474~480 (2009), 대한의학회
  9. Hong, J. J., "Enteral administration of a synthetic monoacetyldiglyceride improves survival in a murine model of abdominal sepsis", J. Trauma, 68, pp.62~68 (2010)
  10. Shin, I. S., "EC-18, a synthetic monoacetyldiglyceride (1-palmitoyl-2-linoleoyl-3-acetylglycerol), attenuates the asthmatic response in an aluminum hydroxide", ovalbumin-induced model of asthma1, 2014, pp.18, 116~123
  11. Coffman, R. L., "Converging discoveries: the first reports of IL-4", J. Immunol, 190, pp.847~848 (2013)
  12. Van Dyken, S. J., "Interleukin-4-interleukin-13-mediated alternatively activated macrophages:roles in homeostasis disease", Annu. Rev. Immunol, 31, pp.317~343 (2013)
  13. Sehra, S., "IL-4regulates skin homeostasis the predisposition toward allergic skin inflammation", J. Immunol, 184, pp.3186~3190 (2010)
  14. Hatano, Y., "The Th2 cytokine, interleukin-4, abrogates the cohesion of normal stratum corneum in mice: implications for pathogenesis of atopic dermatitis", Exp. Dermatol, 22, pp.30~35 (2013)
  15. Bao, L., "IL-4 regulates chemokine CCL26 in keratinocytes through the Jak1, 2", Stat6 signal transduction pathway: Implication for atopic dermatitis, 2012, pp.50, 91~97
  16. Brandt, E. B., "Th2 Cytokines Atopic Dermatitis", J. Clin. Cell. Immunol, 2 (2011)
  17. Zhu, N., "Association between the polymorphisms of interleukin-4, the interleukin-4 receptor gene asthma", Chin. Med. J, 126, pp.2943~2951 (2013)
  18. Nie, W., "Association between interleukin-4 receptor alpha chain (IL4RA) I50V Q551R polymorphisms asthma risk: an update meta-analysis", PLoS One, 8, pp.e69120~ (2013)
  19. Schuijs, M. J., "Cytokine targets in airway inflammation", Curr. Opin. Pharmacol, 13, pp.351~361 (2013)
  20. Egawa, M., "Inflammatory monocytes recruited to allergic skin acquire an anti-inflammatory M2 phenotype via basophil-derived interleukin-4", Immunity, 38, pp.570~580 (2013)
  21. Burton, O. T., "Direct effects of IL-4 on mast cells drive their intestinal expansion increase susceptibility to anaphylaxis in a murine model of food allergy", Mucosal Immunol, 6, pp.740~750 (2013)
  22. Kaplan, M. H., "Stat6 is required for mediating responses to IL-4 for development of Th2 cells", Immunity, 4, pp.313~319 (1996)
  23. Schoenborn, J. R., "Regulation of interferon-gamma during innate adaptive immune responses", Adv. Immunol, 96, pp.41~101 (2007)
  24. Hu, X., "Cross-regulation of signaling pathways by interferon-gamma : implications for immune responses autoimmune diseases", Immunity, 31, pp.539~550 (2009)
  25. Wick, K. R., "IL-4 induces serine phosphorylation of the STAT6 transactivation domain in B lymphocytes", Mol. Immunol, 37, pp.641~652 (2000)
  26. Wu, F., "Deer antler base as a traditional Chinese medicine:a review of its traditional uses, chemistry pharmacology", J. Ethnopharmacol, 145, pp.403~415 (2013)
  27. Gilbey, A., "Health benefits of deer elk velvet antler supplements: a systematic review of randomised controlled studies", N. Z. Med. J, 125, pp.80~86 (2012)
  28. Mushaben, E. M., "Rapamycin attenuates airway hyperreactivity, goblet cells, IgE in experimental allergic asthma", J. Immunol, 187, pp.5756~5763 (2011)
  29. Geha, R. S., "The regulation of immunoglobulin E class-switch recombination", Nat. Rev. Immunol, 3, pp.721~732 (2003)
  30. Cookson, W., "The immunogenetics of asthma eczema:a new focus on the epithelium", Nat. Rev. Immunol, 4, pp.978~988 (2004)
  31. Li, L., "IL-4 utilizes an alternative receptor to drive apoptosis of Th1 cells skews neonatal immunity toward Th2", Immunity, 20, pp.429~440 (2004)
  32. Liew, F. Y., "T(H)1 T(H)2 cells: a historical perspective", Nat. Rev. Immunol, 2, pp.55~60 (2002)
  33. Yang, X. O., "The signaling suppressor CIS controls proallergic T cell development allergic airway inflammation", Nat. Immunol, 14, pp.732~740 (2013)
  34. Knosp, C. A., "SOCS2regulates T helper type 2 differentiation the generation of type 2 allergic responses", J. Exp. Med, 208, pp.1523~1531 (2011)
  35. Biswas, S. K., "Macrophage plasticity interaction with lymphocyte subsets: cancer as a paradigm", Nat. Immunol, 11, pp.889~896 (2010)
  36. Coffman, R. L., "Origins of the T(H)1-T(H)2 model: a personal perspective", Nat. Immunol, 7, pp.539~541 (2006)
  37. Sykes, A., "Rhinovirus 16-induced IFN-alpha IFN-beta are deficient in bronchoalveolar lavage cells in asthmatic patients", J. Allergy Clin. Immunol, 129, pp.1506~1514 (2012)
  38. Baraldo, S., "Deficient antiviral immune responses in childhood: distinct roles of atopy asthma", J. Allergy Clin. Immunol, 130, pp.1307~1314 (2012)
  39. Huber, J. P., "Cutting edge: Type I IFN reverses human Th2 commitment stability by suppressing GATA3", J. Immunol, 185, pp.813~817 (2010)

관련 논문AI추천

Effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on Immune Functions in Healthy Adults in a Randomized Controlled Trial김상환, 김영준, 김재화, 손기영, 윤선영, 정새호, 정진선, 한용해, 황희진대한면역학회 · Immune Network2015 · 제15권 제3호Role of Salvia miltiorrhiza for Modulation of Th2-derived Cytokines in the Resolution of Inflammation김경제, 김설아, 문선희, 신슬미, 오희은, 이승정, 한신하대한면역학회 · Immune Network2011 · 제11권 제5호Isoegomaketone Ameliorates Atopic Dermatitis via MAPK and STAT Pathway-based Pro-Inflammatory Cytokine Regulation김예람, 신재영, 조병옥, 진창현, 한아름(사)한국방사선산업학회 · 방사선산업학회지2023 · 제17권 제4호N-acetyl-L-alanine ameliorates atopic dermatitis-like symptoms by suppressing Th2 differentiation in DNFB-induced NC/Nga miceHwa-Ryung Song, Hyung-Jin Lim, Jiaying Bao, Jong-Suk Kim, Myung-Kwan Han, Seung-Gook Kim, Suhong Duan, Uyanga TSogt생화학분자생물학회 · BMB Reports2025 · 제58권 제10호Leukotriene B4 receptors contribute to house dust mite-induced eosinophilic airway inflammation via TH2 cytokine productionDonghwan Park, Dong-Wook Kwak, Jae-Hong Kim생화학분자생물학회 · BMB Reports2021 · 제54권 제3호Treatment with phosphodiester CpG-ODN ameliorates atopic dermatitis by enhancing TGF-β signaling김태윤, 방철환, 안은주, Doo-Sik Kim, Eun-Jung Lee, Gaurav Agrahari, Hae-Young Kim, Myung Shin Jeon, Won-Kook Ham생화학분자생물학회 · BMB Reports2021 · 제54권 제2호

이 간행물의 다른 논문 (6건)