Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes

Long Jin, Atsuhito Nakao, Masafumi Nakayama, Noriko Yamaguchi, Yuko Kojima, Nobuhiro Nakano, Ryoji Tsuboi, Ko Okumura, Hideo Yagita, Hideoki Ogawa

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62 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1175-1179
Number of pages5
JournalJournal of Investigative Dermatology
Issue number5
Publication statusPublished - 2004 May
Externally publishedYes


  • Keratinocytes
  • TGF-β

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


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