The effect of nitric oxide on p11 expression was studied in an immortalized human bronchial epithelial cell line (BEAS-2B cells). Three nitric oxide donors were used: spermine NONOate (SP), (؎)-S-nitroso-N-acetylpenicillamine (SNAP), and S-nitrosoglutathione (SNOG). All three nitric oxide donors had similar effects resulting in dose-dependent and time-dependent accumulation of p11 protein and an increase of steady-state p11 mRNA. Studies using a reporter gene containing the region from ؊1499 to ؉89 of the p11 promoter demonstrated an increase in transcriptional activity after stimulation with NO donors for 4 h. These effects were abolished at the promoter and protein level using protein kinase G inhibitors (KT5823 and R p -8-pCPT-cGMPS). Incubation of transfected cells with a cell permeable cGMP analogue (8-Br-cGMP) resulted in a doserelated increase of promoter activity. An electrophoretic mobility shift assay of nuclear proteins extracted from BEAS-2B cells identified an AP-1 site located at ؊82 to ؊77 of the p11 promoter region as an NO-and cGMP-dependent response element. These data were confirmed using a c-jun dominant negative mutant vector and a c-jun expression plasmid. Therefore, we conclude that nitric oxide-induced p11 expression in human bronchial epithelial cells is mediated at least in part through increased binding of activator protein one to the p11 promoter.S-100 proteins are a family of proteins first described by Moore et al. (1) who initially characterized a group of low molecular weight (10,000-12,000) acidic proteins in neural tissue. The S-100 group consists of calcium-binding proteins that are expressed in a cell type-dependent fashion. There are at least 13 members, including S-100a, S-100b, and p11 (calpactin light chain). While p11 is a member of the S-100 family, it does not have the ability to bind Ca ϩ2 ions due to crucial amino acid deletions and substitutions in the two EF-hand loops of the protein (2). p11 binds to and inhibits the phosphorylation of annexin II, and binds to the carboxyl region and inhibits cytosolic phospholipase A 2 activity (3). p11-annexin II tetramer is also reported to be a binding protein for cathepsin B, facilitating tumor invasion and metastasis.Nitric oxide is a lipophilic, short-lived, highly reactive free radical, pluripotent molecule involved in the regulation of blood pressure, neurotransmisson, immune function, arachidonic acid metabolism, cell migration, learning and memory, hormone release, cell differentiation, and cell migration (4). Moreover, nitric oxide also plays a role as a messenger in a number of diseases including septic shock, stroke, diabetes mellitus, and rheumatoid arthritis (5). The main source of NO in humans is nitric oxide synthase (present in at least three isoforms), which catalyzes the oxidation of L-arginine to L-citrulline and NO (6). Nitric oxide influences the expression of many genes including cyclooxygenase-2 (7), tumor necrosis factor-␣ (8), interleukin-8 (9), and interleukin-6 (10). Nitric oxide activates soluble, N...

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