TY - JOUR
T1 - Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes
AU - Jin, Long
AU - Nakao, Atsuhito
AU - Nakayama, Masafumi
AU - Yamaguchi, Noriko
AU - Kojima, Yuko
AU - Nakano, Nobuhiro
AU - Tsuboi, Ryoji
AU - Okumura, Ko
AU - Yagita, Hideo
AU - Ogawa, Hideoki
N1 - Funding Information:
We thank Hiroko Ushio, Chiharu Nishiyama, Keiko Maeda, Toshiro Takai, and Tomoko Tokura for discussion and technical assistance, and Emiko Kawasaki and Michiyo Matsumoto for secretarial assistance. This work was supported in part by the grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
PY - 2004/5
Y1 - 2004/5
N2 - TNF-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family, is a multifunctional cytokine that regulate cellular proliferation, angiogenesis, inflammation, and apoptosis. In this study, we investigated the effect of TWEAK on human keratinocytes. Primary cultured normal human keratinocytes constitutively expressed a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), and produced regulated on activation, normal T expressed and secreted (RANTES) upon TWEAK stimulation in a concentration-dependent manner. The TWEAK-induced RANTES production was abrogated by anti-Fn14 antibody, and synergistically augmented by simultaneous stimulation with transforming growth factor-β. In addition, human keratinocytes differentiated in vitro with high Ca2+-containing medium showed enhanced production of RANTES upon TWEAK stimulation. Furthermore, TWEAK induced rapid phosphorylation of IκB-α in human keratinocytes. Collectively, TWEAK acts on human keratinocytes as an inducer of RANTES via Fn14. Because RANTES has been implicated in inflammation, TWEAK/Fn14 interaction in human keratinocytes may be involved in the pathophysiology of inflammatory skin disorders.
AB - TNF-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family, is a multifunctional cytokine that regulate cellular proliferation, angiogenesis, inflammation, and apoptosis. In this study, we investigated the effect of TWEAK on human keratinocytes. Primary cultured normal human keratinocytes constitutively expressed a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), and produced regulated on activation, normal T expressed and secreted (RANTES) upon TWEAK stimulation in a concentration-dependent manner. The TWEAK-induced RANTES production was abrogated by anti-Fn14 antibody, and synergistically augmented by simultaneous stimulation with transforming growth factor-β. In addition, human keratinocytes differentiated in vitro with high Ca2+-containing medium showed enhanced production of RANTES upon TWEAK stimulation. Furthermore, TWEAK induced rapid phosphorylation of IκB-α in human keratinocytes. Collectively, TWEAK acts on human keratinocytes as an inducer of RANTES via Fn14. Because RANTES has been implicated in inflammation, TWEAK/Fn14 interaction in human keratinocytes may be involved in the pathophysiology of inflammatory skin disorders.
KW - Keratinocytes
KW - RANTES
KW - TGF-β
KW - TWEAK
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U2 - 10.1111/j.0022-202X.2004.22419.x
DO - 10.1111/j.0022-202X.2004.22419.x
M3 - Article
C2 - 15140220
AN - SCOPUS:2442591431
VL - 122
SP - 1175
EP - 1179
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 5
ER -