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

Research output: Contribution to journalArticle

57 Citations (Scopus)

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
Publication statusPublished - Jun 1 1996
Externally publishedYes

Fingerprint

Tacrolimus
Immunosuppressive Agents
Interleukin-6
Transcription Factors
Kidney
T-Lymphocytes
Mesangial Cells
Glomerulonephritis
Fibroblasts
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Immunosuppressant FK506 induces interleukin-6 production through the activation of transcription factor nuclear factor (NF)-κB implications for FK506 nephropathy. / Muraoka, Kei Ichi; Fujimoto, Koutaro; Sun, Xiangao; Yoshioka, Katsuji; Shimizu, Kou Ichi; Yagi, Masao; Bose, Henry; Miyazaki, Itsuo; Yamamoto, Ken-ichi.

In: Journal of Clinical Investigation, Vol. 97, No. 11, 01.06.1996, p. 2433-2439.

Research output: Contribution to journalArticle

Muraoka, Kei Ichi ; Fujimoto, Koutaro ; Sun, Xiangao ; Yoshioka, Katsuji ; Shimizu, Kou Ichi ; Yagi, Masao ; Bose, Henry ; Miyazaki, Itsuo ; Yamamoto, Ken-ichi. / Immunosuppressant FK506 induces interleukin-6 production through the activation of transcription factor nuclear factor (NF)-κB implications for FK506 nephropathy. In: Journal of Clinical Investigation. 1996 ; Vol. 97, No. 11. pp. 2433-2439.
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