Details

Autor(en) / Beteiligte

• Park, Keunhee
• Park, Joo‐Hong
• Yang, Wook‐Jin
• Lee, Jong‐Joo
• Song, Min‐Ji
• Kim, Hyoung‐Pyo

Titel

Transcriptional activation of the IL31 gene by NFAT and STAT6

Ist Teil von

• Journal of leukocyte biology, 2012-02, Vol.91 (2), p.245-257

Ort / Verlag

United States: Society for Leukocyte Biology

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• NFAT and STAT6 play critical roles as positive regulators in calcium‐ and IL‐4‐mediated induction of IL‐31 gene in Th2 and mast cells. 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.