Treatment of OM10.1 cells latently infected with human immunodeficiency virus type 1 (HIV-1) with phorbol ester and calcium ionophore (A23187) induced virus replication which was blocked by N-Ac-Leu-Leu-norleucinal (ALLnL), a calpain inhibitor 1, and not by lactacystin, a specific proteasome inhibitor. When the purified NF-kappaB/IkappaB complex was treated with mu-calpain, the specific DNA-binding activity was demonstrated by using electrophoretic mobility shift assay in vitro. This effect of mu-calpain was inhibited by ALLnL and calpastatin and not by lactacystin. In fact, we found that mu-calpain efficiently degraded IkappaBalpha. Furthermore, our Western blotting analysis has revealed that mu-calpain cleaves IkappaBalpha at its N-terminal and C-terminal regions that were previously reported to be involved in the interaction with NF-kappaB p65. These observations indicate that in monocyte/macrophage cells calcium signaling is involved in NF-kappaB activation through activation of calpain and thus calpain inhibitors may be effective in inhibiting the activation of latently infected HIV. (C) 2003 Elsevier Science (USA). All rights reserved.