Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes.
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-beta. In addition, human keratinocytes differentiated in vitro with high Ca(2+)-containing medium showed enhanced production of RANTES upon TWEAK stimulation. Furthermore, TWEAK induced rapid phosphorylation of IkappaB-alpha 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.
Jin
Long
L
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.
Nakao
Atsuhito
A
Nakayama
Masafumi
M
Yamaguchi
Noriko
N
Kojima
Yuko
Y
Nakano
Nobuhiro
N
Tsuboi
Ryoji
R
Okumura
Ko
K
Yagita
Hideo
H
Ogawa
Hideoki
H
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism*; D000074049:Cytokine TWEAK; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D000074050:TWEAK Receptor; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D048069:Tumor Necrosis Factors
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D018946:Chemokine CCL5; D000074049:Cytokine TWEAK; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D016212:Transforming Growth Factor beta; D048069:Tumor Necrosis Factors; D000072000:NF-KappaB Inhibitor alpha