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. 1996 Jun 1;97(11):2433–2439. doi: 10.1172/JCI118690

Immunosuppressant FK506 induces interleukin-6 production through the activation of transcription factor nuclear factor (NF)-kappa(B). Implications for FK506 nephropathy.

K Muraoka 1, K Fujimoto 1, X Sun 1, K Yoshioka 1, K Shimizu 1, M Yagi 1, H Bose Jr 1, I Miyazaki 1, K Yamamoto 1
PMCID: PMC507328  PMID: 8647935

Abstract

FK506 is a powerful immunosuppressive drug currently in use that inhibits the activation of several transcription factors (nuclear factor (NF)-AT and NF-kappaB) critical for T cell activation. We show here that, contrary to the situation in T cells, FK506 activates transcription factor NF-kappaB in nonlymphoid cells such as fibroblasts and renal mesangial cells. We further show that FK506 induces NF-kappaB-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-kappaB activation/IL-6 production and some of FK506-induced renal abnormalities.

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Selected References

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