Effect of glucocorticoids on the synthesis of antimicrobial peptides in amphibian skin.
Gene-encoded peptide antibiotics are widespread in insects, plants and vertebrates and confer protection against bacterial and fungal infections. NF-kappaB is an important transcription factor for many immunity-related mammalian proteins and also for insect immune genes. The activity of NF-kappaB is regulated by the interaction with an inhibitor, I kappaB. It was recently demonstrated that glucocorticoids induce the synthesis of I kappaB in human cell lines. So far, all genes for peptide antibiotics have promoter motifs with NF-kappaB binding sites, but its actual function in peptide regulation has been studied only in insects. Here we show that glucocorticoid treatment of the frog Rana esculenta inhibits the transcription of all genes encoding antibacterial peptides by inducing the synthesis of I kappaB alpha. These results suggest that also in vertebrates peptide-mediated innate immunity is controlled by NF-kappaB-regulated transcription.
Simmaco
M
M
Dipartimento di Scienze Biomediche, Università di Chieti, Italy.
Boman
A
A
Mangoni
M L
ML
Mignogna
G
G
Miele
R
R
Barra
D
D
Boman
H G
HG
D029845:Amphibian Proteins; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004558:Electric Stimulation; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D011893:Rana esculenta / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects
D029845:Amphibian Proteins; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010455:Peptides; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D014157:Transcription Factors; C092874:esculentin protein, Rana esculenta; D000072000:NF-KappaB Inhibitor alpha; D051841:Transcription Factor RelB