An essential amino acid induces epithelial beta -defensin expression.
Antimicrobial peptides constitute an important component of the mammalian innate immune response. Several types of antimicrobial peptides, including the beta-defensins, are produced at epithelial surfaces in response to infectious threats. Here we show that a class of small molecules, including l-isoleucine and several of its analogs, can specifically induce epithelial beta-defensin expression. This induction is transcriptional in nature and involves activation of the NF-kappaB/rel family of trans-activating factors. We hypothesize that these substances represent unique markers for the presence of pathogens and are recognized by innate immune pattern recognition receptors. Isoleucine or its analogs ultimately may have clinical utility as novel immunostimulants that could bolster the barrier defenses of mucosal surfaces.
Fehlbaum
P
P
Magainin Research Institute and Magainin Pharmaceuticals Inc., 5110 Campus Drive, Plymouth Meeting, PA 19462, USA.
Rao
M
M
Zasloff
M
M
Anderson
G M
GM
D000818:Animals; D002417:Cattle; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D007532:Isoleucine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D023083:beta-Defensins / Q000235:genetics*
D016328:NF-kappa B; D023083:beta-Defensins; D007532:Isoleucine