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Transcriptional activation of the IL31 gene by NFAT and STAT6

Authors
 Keunhee Park  ;  Joo-Hong Park  ;  Wook-Jin Yang  ;  Jong-Joo Lee  ;  Min-Ji Song  ;  Hyoung-Pyo Kim 
Citation
 Journal of Leukocyte Biology, Vol.91(2) : 245-257, 2012 
Journal Title
 Journal of Leukocyte Biology 
ISSN
 0741-5400 
Issue Date
2012
MeSH
Animals ; Base Sequence ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/metabolism ; Calcium/physiology ; Dinitrophenols/pharmacology ; HEK293 Cells/drug effects ; HEK293 Cells/metabolism ; Humans ; Interleukin-4/pharmacology ; Interleukins/biosynthesis ; Interleukins/genetics* ; Ionomycin/pharmacology ; Jurkat Cells/drug effects ; Jurkat Cells/metabolism ; Male ; Mast Cells/drug effects ; Mast Cells/metabolism ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; NFATC Transcription Factors/physiology* ; Promoter Regions, Genetic ; Rats ; Recombinant Fusion Proteins/biosynthesis ; Recombinant Fusion Proteins/genetics ; Regulatory Sequences, Nucleic Acid ; STAT6 Transcription Factor/physiology* ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Serum Albumin/pharmacology ; Tetradecanoylphorbol Acetate/pharmacology ; Transcription, Genetic
Keywords
Animals ; Base Sequence ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/metabolism ; Calcium/physiology ; Dinitrophenols/pharmacology ; HEK293 Cells/drug effects ; HEK293 Cells/metabolism ; Humans ; Interleukin-4/pharmacology ; Interleukins/biosynthesis ; Interleukins/genetics* ; Ionomycin/pharmacology ; Jurkat Cells/drug effects ; Jurkat Cells/metabolism ; Male ; Mast Cells/drug effects ; Mast Cells/metabolism ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; NFATC Transcription Factors/physiology* ; Promoter Regions, Genetic ; Rats ; Recombinant Fusion Proteins/biosynthesis ; Recombinant Fusion Proteins/genetics ; Regulatory Sequences, Nucleic Acid ; STAT6 Transcription Factor/physiology* ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Serum Albumin/pharmacology ; Tetradecanoylphorbol Acetate/pharmacology ; Transcription, Genetic
Abstract
IL-31, a newly identified member of the IL-6 cytokine family, is involved in many pathological conditions, including atopic dermatitis and pruritis. In this study, we investigated how expression of IL-31 is regulated in T cells and mast cells. We observed that expression of IL-31 required a calcium signal and was dependent on the calcineurin-NFAT signaling pathway. Moreover, we found that IL-31 promoter contains a positive regulatory region that mediates calcium- and IL-4-dependent induction of the IL-31 gene and demonstrated that a change into an open chromatin conformation occurs in this region after stimulation with calcium and IL-4. Whereas IL-4 responsiveness required STAT6 binding sites, calcium responsiveness of IL-31 promoter required NFAT binding sites that bind NFATc1 and NFATc2 in vitro and in vivo. The induction of IL-31 promoter activity was impaired when these sites were mutated but was enhanced by CA-NFATc1 or STAT6 proteins and further increased synergistically by combinations of both proteins. Furthermore, the importance of STAT6 proteins was indicated by impaired, IL-4-mediated induction of IL-31 in STAT6-diminished Jurkat cells. Thus, our data demonstrate that calcium and IL-4 signals are required to mediate induction of IL-31 in Th2 cells and mast cells and that this induction appears to result from specific binding of NFAT and STAT6 proteins.
Full Text
http://www.jleukbio.org/content/91/2/245.long
DOI
22045870
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
Park, Keun Hee(박근희)
Park, Joo Hong(박주홍)
Song, Min Ji(송민지)
Lee, Jong Joo(이종주)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90938
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