Published in Volume
97, Issue 11 (June 1, 1996)
J Clin Invest. 1996;97(11):2433–2439.
doi:10.1172/JCI118690.
Copyright ©
1996, The American Society for
Clinical Investigation.
Research Article
Immunosuppressant FK506 induces interleukin-6 production through the activation of transcription factor nuclear factor (NF)-kappa(B). Implications for FK506 nephropathy.
K Muraoka, K Fujimoto, X Sun, K Yoshioka, K Shimizu, M Yagi, H Bose, Jr, I Miyazaki and K Yamamoto
Department of Molecular Pathology, Cancer Research Institute, School of Medicine, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920, Japan.
Published June 1, 1996
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.
