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Difference in the Transcriptional Activity of the Interleukin-4 Promoter Haplotypes

Korean Journal of Pediatrics 2005;48(5):495-499.
Published online May 15, 2005.
Difference in the Transcriptional Activity of the Interleukin-4 Promoter Haplotypes
Eun Hwa Choi1, Hee Sup Kim2, Stephen J. Chanock2, Hoan Jong Lee1
1Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
1Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
2Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health
2Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health
Interleukin-4 유전자의 Promoter 일배체형에 따른 전사능의 차이
최은화1, 김희섭2, Stephen J. Chanock2, 이환종1
1서울대학교 의과대학 소아과학교실
1서울대학교 의과대학 소아과학교실
2Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health
2Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health
Correspondence: 
Hoan Jong Lee, Email: hoanlee@snu.ac.kr
Abstract
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.
Key Words: Respiratory syncytial virus , Transcriptional activation , Interleukin 4 , Haplotype


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