Production of β-defensins by human airway epithelia

被引:493
作者
Singh, PK
Jia, HP
Wiles, K
Hesselberth, J
Liu, LD
Conway, BAD
Greenberg, EP
Valore, EV
Welsh, MJ
Ganz, T
Tack, BF
McCray, PB [1 ]
机构
[1] Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Pediat, Iowa City, IA 52242 USA
[2] Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Internal Med, Iowa City, IA 52242 USA
[3] Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Microbiol, Iowa City, IA 52242 USA
[4] Univ Calif Los Angeles, Sch Med, Will Rogers Inst Pulm Res, Los Angeles, CA 90095 USA
关键词
D O I
10.1073/pnas.95.25.14961
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-1 beta 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.
引用
收藏
页码:14961 / 14966
页数:6
相关论文
共 30 条
[11]   ELEMENTAL COMPOSITION OF HUMAN AIRWAY SURFACE FLUID IN HEALTHY AND DISEASED AIRWAYS [J].
JORIS, L ;
DAB, I ;
QUINTON, PM .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1993, 148 (06) :1633-1637
[12]   Ion composition of airway surface liquid of patients with cystic fibrosis as compared with normal and disease-control subjects [J].
Knowles, MR ;
Robinson, JM ;
Wood, RE ;
Pue, CA ;
Mentz, WM ;
Wager, GC ;
Gatzy, JT ;
Boucher, RC .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (10) :2588-2595
[13]  
KONDO M, 1991, AM J PHYSIOL, V263, pL105
[14]   DEFENSINS - ANTIMICROBIAL AND CYTOTOXIC PEPTIDES OF MAMMALIAN-CELLS [J].
LEHRER, RI ;
LICHTENSTEIN, AK ;
GANZ, T .
ANNUAL REVIEW OF IMMUNOLOGY, 1993, 11 :105-128
[15]   Structure and mapping of the human β-defensin HBD-2 gene and its expression at sites of inflammation [J].
Liu, L ;
Wang, LN ;
Jia, HP ;
Zhao, CQ ;
Heng, HHQ ;
Schutte, BC ;
McCray, PB ;
Ganz, T .
GENE, 1998, 222 (02) :237-244
[16]   The human beta-defensin-1 and alpha-defensins are encoded by adjacent genes: Two peptide families with differing disulfide topology share a common ancestry [J].
Liu, LD ;
Zhao, CQ ;
Heng, HHQ ;
Ganz, T .
GENOMICS, 1997, 43 (03) :316-320
[17]   Human airway epithelia express a beta-defensin [J].
McCray, PB ;
Bentley, L .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1997, 16 (03) :343-349
[18]   Localization of human intestinal defensin 5 in Paneth cell granules [J].
Porter, EM ;
Liu, L ;
Oren, A ;
Anton, PA ;
Ganz, T .
INFECTION AND IMMUNITY, 1997, 65 (06) :2389-2395
[19]   Coordinate induction of two antibiotic genes in tracheal epithelial cells exposed to the inflammatory mediators lipopolysaccharide and tumor necrosis factor alpha [J].
Russell, JP ;
Diamond, G ;
Tarver, AP ;
Scanlin, TF ;
Bevins, CL .
INFECTION AND IMMUNITY, 1996, 64 (05) :1565-1568
[20]   Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid [J].
Smith, JJ ;
Travis, SM ;
Greenberg, EP ;
Welsh, MJ .
CELL, 1996, 85 (02) :229-236