INDUCIBLE EXPRESSION OF AN ANTIBIOTIC PEPTIDE GENE IN LIPOPOLYSACCHARIDE-CHALLENGED TRACHEAL EPITHELIAL CELLS

Mammals continually confront microbes at mucosal surfaces. A current m odel suggests that epithelial cells contribute to defense at these sit es, in part through the production of broad-spectrum antibiotic peptid es. Previous studies have shown that invertebrates can mount a host de fense response characterized by the induction in epithelial cells of a variety of antibiotic proteins and peptides when they are challenged with microorganisms, bacterial cell wall/membrane components, or traum atic injury [Boman, H.G. & Hultmark, D. (1987) Annu. Rev. Microbiol. 4 1, 103-126]. However, factors that govern the expression of similar de fense molecules in mammalian epithelial cells are poorly understood. H ere, a 13-fold induction of the endogenous gene encoding tracheal anti microbial peptide was found to characterize a host response of trachea l epithelial cells (TECs) exposed to bacterial lipopolysaccharide (LPS ). Northern blot data indicated that TECs express CD14, a well-charact erized LPS-binding protein known to mediate many LPS responses. A mono clonal antibody to CD14 blocked the observed tracheal antimicrobial pe ptide induction by LPS under serum-free conditions. Together the data support that CD14 of epithelial cell origin mediates the LPS induction of an antibiotic peptide gene in TECs, providing evidence for the act ive participation of epithelial cells in the host's local defense resp onse to bacteria. Furthermore, the data allude to a conservation of th is host response in evolution and suggest that a similar inducible pat hway of host defense is prevalent at mucosal surfaces of mammals.