title: Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes.
abstract: 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.
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Long
authors.initials: L
authors.lastname: Jin
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Nakao
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kojima
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakano
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tsuboi
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
mesh_terms: 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
chemical_list: 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