1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) Modulates Th2 Immunity through Attenuation of IL-4 Expression.
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.
ENZYCHEM Lifesciences, Daejeon 305-732, Korea.
Sun Young
SY
Yoon
Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
Ho Bum
HB
Kang
Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
Young-Eun
YE
Ko
Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea. ; Soonchunhyang Medical Science Research Institute, College of Medicine Soonchunhyang University, Cheonan 330-721, Korea.
Su-Hyun
SH
Shin
Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
Young-Jun
YJ
Kim
ENZYCHEM Lifesciences, Daejeon 305-732, Korea.
Ki-Young
KY
Sohn
ENZYCHEM Lifesciences, Daejeon 305-732, Korea.
Yong-Hae
YH
Han
ENZYCHEM Lifesciences, Daejeon 305-732, Korea.
Saeho
S
Chong
Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
Jae Wha
JW
Kim
EC-18; IL-4; STAT6; Th2 modulator