Interleukin-17 augments tumor necrosis factor-alpha-induced granulocyte and granulocyte/macrophage colony-stimulating factor release from human colonic myofibroblasts.
BACKGROUND
Interleukin (IL)-17 is a newly identified T-cell-specific cytokine. In this study, we investigated the effects of IL-17 on colony-stimulating factor (CSF) release in human colonic subepithelial myofibroblasts (SEMFs).


METHODS
CSF release and mRNA expression were determined by enzyme-linked immunosorbent assay (ELISA) and Northern blotting, respectively. Nuclear factor (NF)-kappaB- and activating protein (AP-1)-DNA binding activities were evaluated by electrophoretic gel mobility shift assays (EMSAs).


RESULTS
Unstimulated cells secreted a small amount of granulocyte G- and granulocyte/macrophage (GM)-CSF, and a considerable amount of M-CSF. IL-17 weakly enhanced G-CSF release, but did not affect GM- and M-CSF release. IL-17 selectively enhanced tumor necrosis factor (TNF)-alpha-induced G- and GM-CSF release. The combination of IL-17 plus TNF-alpha induced a marked increase in NF-kappaB- and AP-1-DNA binding activities. The adenovirus-mediated transfer of a stable form of IkappaBalpha and/or a dominant negative mutant of c-Jun markedly inhibited the IL-17 plus TNF-alpha-induced G- and GM-CSF mRNA expression. Furthermore, a stability study showed that IL-17 plus TNF-alpha markedly enhanced the stability of G- and GM-CSF mRNA.


CONCLUSIONS
IL-17 augments TNF-alpha-induced G- and GM-CSF release via transcriptional and posttranscriptional mechanisms.
Andoh
Akira
A
Department of Internal Medicine, Shiga University of Medical Science, Seta Tukinowa, Otsu, 520-2192, Japan.
Yasui
Hirofumi
H
Inatomi
Osamu
O
Zhang
Zhuobin
Z
Deguchi
Yasuyuki
Y
Hata
Kazunori
K
Araki
Yoshio
Y
Tsujikawa
Tomoyuki
T
Kitoh
Katsuyuki
K
Kim-Mitsuyama
Shokei
S
Takayanagi
Atsushi
A
Shimizu
Nobuyoshi
N
Fujiyama
Yoshihide
Y
D015152:Blotting, Northern; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D016328:NF-kappa B / Q000032:analysis; D018808:Transcription Factor AP-1 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D003115:Colony-Stimulating Factors; D004268:DNA-Binding Proteins; D020381:Interleukin-17; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha