SURFACTANT PROTEIN-A ACTIVATES NF-KAPPA-B IN THE THP-1 MONOCYTIC CELL-LINE

The expression of many genes for which products are involved in inflam mation is controlled by the transcriptional regulator nuclear factor ( NF)-kB. Because surfactant protein (SP) A is involved in local host de fense in the lung and alters immune cell, function by modulating the e xpression of proinflammatory cytokines as well as surface proteins inv olved in inflammation, we hypothesized that SP-A exerts its action, at least in part, via activation of NF-kB. We used gel shift assays to d etermine whether SP-A activated NF-kB in the THP-1 cell line,a human m onocytic cell line. Activation of NF-KB in THP-1 cells by SP-A doses a s low as 1 mu g/ml occurred within 30 min of SP-A treatment, peaked at 60 min, and then declined. This activation is inhibited by known inhi bitors of NF-kB or by simultaneous treatment of the cells with surfact ant lipids. Moreover, the NF-kB inhibitors blocked SP-A-dependent incr eases in tumor necrosis factor-alpha mRNA levels. These observations s uggest a mechanism by which SP-A plays a role in the pathogenesis of s ome lung conditions and point to potential therapeutic measures that c ould be used to prevent SP-A induced inflammation in the lung.