title: Production of beta-defensins by human airway epithelia.
abstract: Human beta-defensins (HBDs) are antimicrobial peptides that may play a role in mucosal defense. Diminished activity of these peptides has been implicated in the pathogenesis of cystic fibrosis (CF) lung disease. We show that HBD-1 and HBD-2 mRNAs are expressed in excised surface and submucosal gland epithelia from non-CF and CF patients. The pro-inflammatory cytokine interleukin-1beta stimulated the expression of HBD-2 but not HBD-1 mRNA and peptide in primary cultures of airway epithelia. HBD-1 was found in bronchoalveolar lavage (BAL) fluid from normal volunteers, CF patients, and patients with inflammatory lung diseases, whereas HBD-2 was detected in BAL fluid from patients with CF or inflammatory lung diseases, but not in normal volunteers. Both HBD-1 and HBD-2 were found in BAL fluid in concentrations of several ng/ml, and both recombinant peptides showed salt-sensitive bactericidal activity. These data suggest that in the lung HBD-2 expression is induced by inflammation, whereas HBD-1 may serve as a defense in the absence of inflammation.
authors.affiliation: Department of Internal Medicine, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Singh
authors.forename: H P
authors.initials: HP
authors.lastname: Jia
authors.forename: K
authors.initials: K
authors.lastname: Wiles
authors.forename: J
authors.initials: J
authors.lastname: Hesselberth
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: B A
authors.initials: BA
authors.lastname: Conway
authors.forename: E P
authors.initials: EP
authors.lastname: Greenberg
authors.forename: E V
authors.initials: EV
authors.lastname: Valore
authors.forename: M J
authors.initials: MJ
authors.lastname: Welsh
authors.forename: T
authors.initials: T
authors.lastname: Ganz
authors.forename: B F
authors.initials: BF
authors.lastname: Tack
authors.forename: P B
authors.initials: PB
authors.lastname: McCray
mesh_terms: D002478:Cells, Cultured; D023082:Defensins; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000494:pharmacology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis*; D012137:Respiratory System / Q000378:metabolism; D023083:beta-Defensins
chemical_list: C406407:DEFB1 protein, human; D023082:Defensins; D007375:Interleukin-1; D012333:RNA, Messenger; D023083:beta-Defensins