Immunosuppressant FK506 induces interleukin-6 production through the activation of transcription factor nuclear factor (NF)-κB implications for FK506 nephropathy

Kei Ichi Muraoka, Koutaro Fujimoto, Xiangao Sun, Katsuji Yoshioka, Kou Ichi Shimizu, Masao Yagi, Henry Bose, Itsuo Miyazaki, Ken Ichi Yamamoto

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Abstract

FK506 is a powerful immunosuppressive drug currently in use that inhibits the activation of several transcription factors (nuclear factor (NF)-AT and NF-κB) critical for T cell activation. We show here that, contrary to the situation in T cells, FK506 activates transcription factor NF-κB in non-lymphoid cells such as fibroblasts and renal mesangial cells. We further show that FK506 induces NF-κB-regulated IL-6 production in vitro and in vivo, in particular in kidney. IL-6 has been shown previously to produce renal abnormalities in vivo, such as mesangioproliferative glomerulonephritis. Similar renal abnormalities were also observed in FK506-treated animals. These results thus suggest a causal relationship between FK506-induced NF-κB activation/IL-6 production and some of FK506-induced renal abnormalities.

Original languageEnglish
Pages (from-to)2433-2439
Number of pages7
JournalJournal of Clinical Investigation
Volume97
Issue number11
DOIs
Publication statusPublished - Jun 1 1996

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Keywords

  • FK506
  • IL-6
  • Immunosuppressant
  • NF-κB
  • Nephrotoxicity

ASJC Scopus subject areas

  • Medicine(all)

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