K Muraoka, K Fujimoto, X Sun, K Yoshioka, K Shimizu, M Yagi, H Bose, I Miyazaki, K Yamamoto
J Clin Invest.
1996;
97(11):2433–2439
doi:10.1172/JCI118690
This article Copyright © 1996, The American Society for Clinical Investigation
Abstract
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K506 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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