Functional analysis of -351 interleukin-9 promoter polymorphism reveals an activator controlled by NF-κB

作者: S B Early , P Huyett , K Brown-Steinke , L Borish , J W Steinke

DOI: 10.1038/GENE.2009.28

关键词: AlleleTranscription factorGeneBiologyChromatin immunoprecipitationInterleukin 9Molecular biologyGeneticsActivator (genetics)Chromosomal regionTranscription (biology)

摘要: Genetic studies have shown linkages for asthma to the chromosomal region 5q31-q33 in humans that includes IL-9 gene. An A-to-G base substitution has been identified at bp -351 promoter. The role of this polymorphism promoter function was assessed utilizing CD4+ T cells purified from individuals with one or two G alleles comparison those homozygous wild-type A. presence an A (A allele) increased mitogen-stimulated transcription twofold subjects position. Binding nuclear extract proteins IL-9-producing human cell lines DNA sequences including exchange demonstrated specific binding factor NF-kappaB. NF-kappaB confirmed vivo using chromatin immunoprecipitation assay. Recombinant bound a fragment allele fivefold higher affinity than it did allele. Individuals carrying display synthesis IL-9, which may result strong Th2 immune responses and modulation their susceptibility infectious, neoplastic, parasitic atopic disease.

参考文章(35)
Tricia D. LeVan, John W. Bloom, Thomas J. Bailey, Christopher L. Karp, Marilyn Halonen, Fernando D. Martinez, Donata Vercelli, A Common Single Nucleotide Polymorphism in the CD14 Promoter Decreases the Affinity of Sp Protein Binding and Enhances Transcriptional Activity The Journal of Immunology. ,vol. 167, pp. 5838- 5844 ,(2001) , 10.4049/JIMMUNOL.167.10.5838
Vincenzo Casolaro, Rongbing Chen, Santa Jeremy Ono, Steve N. Georas, Zhimin Song, Dimitris Monos, Polymorphic nucleotides within the human IL-4 promoter that mediate overexpression of the gene. Journal of Immunology. ,vol. 156, pp. 424- 429 ,(1996)
Michael Stassen, Christian Müller, Martina Arnold, Lothar Hültner, Stefan Klein-Hessling, Christine Neudörfl, Tanja Reineke, Edgar Serfling, Edgar Schmitt, IL-9 and IL-13 production by activated mast cells is strongly enhanced in the presence of lipopolysaccharide: NF-kappa B is decisively involved in the expression of IL-9. Journal of Immunology. ,vol. 166, pp. 4391- 4398 ,(2001) , 10.4049/JIMMUNOL.166.7.4391
John W. Steinke, Elizabeth Barekzi, James Hagman, Larry Borish, Functional analysis of -571 IL-10 promoter polymorphism reveals a repressor element controlled by sp1. Journal of Immunology. ,vol. 173, pp. 3215- 3222 ,(2004) , 10.4049/JIMMUNOL.173.5.3215
H Merz, FA Houssiau, K Orscheschek, JC Renauld, A Fliedner, M Herin, H Noel, M Kadin, HK Mueller-Hermelink, J Van Snick, Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma. Blood. ,vol. 78, pp. 1311- 1317 ,(1991) , 10.1182/BLOOD.V78.5.1311.1311
Renate G. Nickel, Vincenzo Casolaro, Ulrich Wahn, Kirsten Beyer, Kathleen C. Barnes, Beverly S. Plunkett, Linda R. Freidhoff, Claudia Sengler, James R. Plitt, Robert P. Schleimer, Luis Caraballo, Raana P. Naidu, Paul N. Levett, Terri H. Beaty, Shau-Ku Huang, Atopic Dermatitis Is Associated with a Functional Mutation in the Promoter of the C-C Chemokine RANTES The Journal of Immunology. ,vol. 164, pp. 1612- 1616 ,(2000) , 10.4049/JIMMUNOL.164.3.1612
Jamila Louahed, Abdenaim Kermouni, J. Van Snick, J.-C. Renauld, IL-9 induces expression of granzymes and high-affinity IgE receptor in murine T helper clones. Journal of Immunology. ,vol. 154, pp. 5061- 5070 ,(1995)
L. J. ROSENWASSER, D. J. KLEMM, J. K. DRESBACK, H. INAMURA, J. J. MASCALI, M. KLINNERT, L. BORISH, Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy Clinical & Experimental Allergy. ,vol. 25, pp. 74- 78 ,(1995) , 10.1111/J.1365-2222.1995.TB00428.X
John Kuriyan, Dimitris Thanos, Structure of the NF-κB transcription factor: a holistic interaction with DNA Structure. ,vol. 3, pp. 135- 141 ,(1995) , 10.1016/S0969-2126(01)00143-5