Production of beta-defensins by human airway epithelia.
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.
Singh
P K
PK
Department of Internal Medicine, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
Jia
H P
HP
Wiles
K
K
Hesselberth
J
J
Liu
L
L
Conway
B A
BA
Greenberg
E P
EP
Valore
E V
EV
Welsh
M J
MJ
Ganz
T
T
Tack
B F
BF
McCray
P B
PB
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
C406407:DEFB1 protein, human; D023082:Defensins; D007375:Interleukin-1; D012333:RNA, Messenger; D023083:beta-Defensins