EC-18, a synthetic monoacetyldiglyceride (1-palmitoyl-2-linoleoyl-3-acetylglycerol), attenuates the asthmatic response in an aluminum hydroxide/ovalbumin-induced model of asthma

Shin, In‐Sik; Shin, Na‐Rae; Jeon, Chan‐Mi; Kwon, Ok‐Kyoung; Sohn, Ki-Young; Lee, Tae-Suk; Kim, Jae Wha; Ahn, Ki Hoon; Oh, Sei‐Ryang

doi:10.1016/j.intimp.2013.11.006

Cited by 15 publications

(15 citation statements)

References 19 publications

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“…In a previous report, we showed that EC-18 significantly suppressed the allergic asthma response induced by aluminum hydroxide/ovalbumin in mice and also reduced elevated Th2 cytokines, IgE, IgG, and eotaxin-1 levels ( 10 ). It is well known Th2 cytokines, such as IL-4, IL-5, and IL-13, play an important role in the initiation and progression of atopic dermatitis ( 28 ).…”

Section: Discussionmentioning

confidence: 92%

“…It has been used as a biological activator and dieted preferentially as a valid remedy over 20 centuries ( 26 , 27 ). EC-18 has been identified as a main component of an extract that has a biological effect on immune modulation ( 4 , 7 , 9 , 10 ), and it has been synthesized as a compound substance to produce new drug ( 5 , 6 ). In this study, the scientific evidence for evaluating EC-18's efficacy in immune modulation was considered.…”

Section: Discussionmentioning

confidence: 99%

“…Hong et al found that EC-18 markedly improved survival in a murine model of abdominal sepsis via immunomodulation ( 9 ). It was recently reported that EC-18 effectively suppressed the allergic asthma response induced by ovalbumin in a murine model ( 10 ). Therefore, EC-18 is considered to be one of the agents with biological activity, such as cytokine modulation ( 9 ), anti-metastatic effects ( 8 ), and hematopoiesis ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

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

Yoon¹,

Kang

Shin

et al. 2015

Immune Netw

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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.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Yoon¹,

Kang

Shin

et al. 2015

Immune Netw

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“…In traditional oriental medicine, extracts from the antlers of Sika deer ( Cervus nippon Temminck) have been extensively used for alleviating various symptoms such as anorexia and fatigue, invigorating vital energy, and nourishing the blood [ 20 ]. In a murine model of ovalbumin (OVA)-induced asthma, PLAG reportedly alleviated the allergic asthma symptoms including the recruitment of inflammatory cells, methacholine responsiveness, mucus overproduction, and T H 2 cytokine production [ 21 ]. It was also recently reported that PLAG modulates T H 2 immunity by reducing the phosphorylation of signal transducer and activator of transcription 6 (STAT6), which inhibits the expression of affected genes such as IL-4 [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells

et al. 2016

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Increased number of eosinophils in the circulation and sputum is associated with the severity of asthma. The respiratory epithelium produces chemokine (C-C motif) ligands (CCL) which recruits and activates eosinophils. A chemically synthesized monoacetyl-diglyceride, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) is a major constituent in the antlers of Sika deer (Cervus nippon Temminck) which has been used in oriental medicine. This study was aimed to investigate the molecular mechanism of PLAG effect on the alleviation of asthma phenotypes. A549, a human alveolar basal epithelial cell, and HaCaT, a human keratinocyte, were activated by the treatment of interleukin-4 (IL-4), and the expression of chemokines, known to be effective on the induction of eosinophil migration was analyzed by RT-PCR. The expression of IL-4 induced genes was modulated by the co-treatment of PLAG. Especially, CCL26 expression from the stimulated epithelial cells was significantly blocked by PLAG, which was confirmed by ELISA. The transcriptional activity of signal transducer and activator of transcription 6 (STAT6), activated by IL-4 mediated phosphorylation and nuclear translocation, was down-regulated by PLAG in a concentration-dependent manner. In ovalbumin-induced mouse model, the infiltration of immune cells into the respiratory tract was decreased by PLAG administration. Cytological analysis of the isolated bronchoalveolar lavage fluid (BALF) cells proved the infiltration of eosinophils was significantly reduced by PLAG. In addition, PLAG inhibited the migration of murine bone marrow-derived eosinophils, and human eosinophil cell line, EoL-1, which was induced by the addition of A549 culture medium.

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“…Hong et al found that PLAG markedly improves survival in a murine model of abdominal sepsis via immunomodulation ( 10 ). It was recently reported that PLAG effectively suppressed the allergic asthma response induced by ovalbumin in a murine model ( 11 ). Generally, the T-helper type 2 (Th2)-driven pheno-type arises from dysregulated innate and adaptive immune responses.…”

Section: Introductionmentioning

confidence: 99%

Effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on Immune Functions in Healthy Adults in a Randomized Controlled Trial

Hwang

Sohn²,

Han³

et al. 2015

Immune Netw

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We previously reported that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) accelerates hematopoiesis and has an improving effect on animal disease models such as sepsis and asthma. The effects of PLAG supplementation on immune modulation were assessed in healthy men and women. The objective was to evaluate the effects of PLAG supplementation on immune regulatory functions such as activities of immune cells and cytokine production. A randomized double blind placebo-controlled trial was conducted. Seventy-five participants were assigned to one of two groups; all participants had an appropriate number of white blood cells on the testing day. The PLAG group (n=27) received oral PLAG supplements and the control group (n=22) received oral soybean oil supplements. IL-4 and IL-6 production by peripheral blood mononuclear cells (PBMC) were lower (p<0.001 and p<0.001, respectively) with PLAG than with soybean oil. However, the production of IL-2 and IFN-γ by PBMC was unaltered with PLAG supplementation. The B cell proliferation decreased significantly in the PLAG group compared to the soybean oil control (p<0.05). The intake of PLAG in healthy adults for 4 weeks was deemed safe. These data suggest that PLAG has an immunomodulatory function that inhibits the excessive immune activity of immunological disorders such as atopic and autoimmune diseases. PLAG could improve the condition of these diseases safely as a health food supplement.

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EC-18, a synthetic monoacetyldiglyceride (1-palmitoyl-2-linoleoyl-3-acetylglycerol), attenuates the asthmatic response in an aluminum hydroxide/ovalbumin-induced model of asthma

Cited by 15 publications

References 19 publications

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

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

PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells

Effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on Immune Functions in Healthy Adults in a Randomized Controlled Trial

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