COORDINATE INDUCTION OF 2 ANTIBIOTIC GENES IN TRACHEAL EPITHELIAL-CELLS EXPOSED TO THE INFLAMMATORY MEDIATORS LIPOPOLYSACCHARIDE AND TUMOR-NECROSIS-FACTOR-ALPHA

Peptides with potent broad-spectrum antibiotic activity have been iden tified in many animal species. Recent investigations have demonstrated that epithelial cells are a site of antibiotic peptide expression, su ggesting that these peptides contribute to host defense at mucosal sur faces. Expression of tracheal antimicrobial peptide (TAP), a member of the beta-defensin family of peptides, is inducible in cultured trache al epithelial cells (TEC) upon challenge with bacterial lipopolysaccha ride (LPS) (G. Diamond, J. P. Russell, and C. L. Bevins, Proc. Natl. A cad. Sci, USA, in press). In this study, an anchored reverse transcrip tase PCR strategy was used to determine if TAP was the sole beta-defen sin isoform expressed upon stimulation of the cells with LPS. In addit ion to TAP, a second class of cDNA clones which encoded lingual antimi crobial peptide (LAP), a beta-defensin peptide recently isolated fi om a different mucosal site, the bovine tongue, was identified (B. S. Sc honwetter, E. D. Stolzenberg, and M. Zasloff, Science 267:1645-1648, 1 995). Northern (RNA) blot analysis demonstrated in vivo expression of LAP mRNA in tracheal mucosa. Levels of LAP mRNA were higher in culture d TEC challenged with either LPS or tumor necrosis factor alpha than i n control cells. Thus, a response of TEC exposed to inflammatory media tors is induction of antibiotic-encoding genes, including both TAP and LAP. This work complements the in vivo studies of Schonwetter et al. (cited above), which showed elevated levels of LAP mRNA in squamous ep ithelial cells of the tongue near sites of tissue injury and inflammat ion, by suggesting possible mediators of the in vivo observation. Toge ther these lines of investigations support the hypothesis that inducib le expression of endogenous antibiotic peptides by inflammatory mediat ors characterizes local defense of mammalian mucosal surfaces.