IL-4 modulates the histamine content of mast cells in a mast cell/fibroblast co-culture through a Stat6 signaling pathway in fibroblasts.
IL-4 plays a crucial role in the pathogenesis of allergic diseases, such as the induction of IgE synthesis and the development of mast cells. To further understand the effect of IL-4 on mast cells in skin, we utilized a mast cell/fibroblast co-culture system as an in vitro model of dermal mast cells. IL-4 induced mast cell growth in the culture with fibroblasts. Immunoblot analysis revealed that IL-4 activated Stat6 in both mast cells and fibroblasts. The over-expression of dominant-negative Stat6 in fibroblasts in the presence of IL-4 decreased the histamine content per mast cell, but not the number of mast cells. In contrast, the over-expression of constitutively-active Stat6 in fibroblasts increased the histamine content per mast cell, indicating that the activation of Stat6 in fibroblasts supports the maturation of mast cells co-cultured with fibroblasts.
Nabeshima
Yukiko
Y
Department of Dermatology, Programs for Biomedical Research, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Hiragun
Takaaki
T
Morita
Eishin
E
Mihara
Shoji
S
Kameyoshi
Yoshikazu
Y
Hide
Michihiro
M
D016475:3T3 Cells; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D050800:STAT6 Transcription Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D006632:Histamine