Smi. Kazmi et al., SUPPRESSION OF NF-KAPPA-B ACTIVATION AND NF-KAPPA-B-DEPENDENT GENE-EXPRESSION BY TEPOXALIN, A DUAL INHIBITOR OF CYCLOOXYGENASE AND 5-LIPOXYGENASE, Journal of cellular biochemistry, 57(2), 1995, pp. 299-310
Tepoxalin, a dual inhibitor of cyclooxygenase (CO) and 5-lipoxygenase
(5LO) with cytokine modifying activity, is also a potent inhibitor of
the transcription factor, nuclear factor kappa B (NF kappa B). NF kapp
a B is a pleiotropic activator that is involved in the regulation of m
any genes whose products participate in immune or inflammatory respons
es. Tepoxalin inhibited in a dose related manner NF kappa B activation
by PMA + ionomycin or H2O2 in Jurkat and HeLa cells. TNF-alpha-induce
d NF kappa B was also inhibited by tepoxalin in HeLa cells, while rela
tively less marked inhibition was observed in jurkat cells. Activation
of NF kappa B in several monocytic cell lines was also suppressed by
tepoxalin. However AP-1 stimulation under the same conditions was not
affected by tepoxalin. Other CO, LO inhibitors such as naproxen or zil
euton did not inhibit NF kappa B activities. This inhibitory activity
of tepoxalin was further illustrated by its suppression of NF kappa B
regulated genes such as IL-6 in PMA stimulated human PBL and c-myc in
IL-2 dependent T cell lines. Tepoxalin also blocked PMA + ionomycin-in
duced I kappa B degradation in a time-dependent fashion. The possible
mechanism of tepoxalin in NF kappa B activation and its potential clin
ical application are discussed. (C) 1995 Wiley-Liss, Inc.