High susceptibility for cystic fibrosis human airway gland cells to produce IL-8 through the IκB kinase α pathway in response to extracellular NaCl content

被引:79
作者
Tabary, O
Escotte, S
Couetil, JP
Hubert, D
Dusser, D
Puchelle, E
Jacquot, J
机构
[1] Ctr Hosp Univ, INSERM, U514, Inst Federatif Rech 53, Reims, France
[2] Hop Cochin, Serv Pneumol, F-75674 Paris, France
[3] Hop Broussais, Dept Chirurg Cardiovasc, F-75674 Paris, France
关键词
D O I
10.4049/jimmunol.164.6.3377
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Increasing evidence suggests that in airways from cystic fibrosis (CP) patients, inflammation may precede bacterial infection and be related to an endogenous dysregulation of proinflammatory cytokines in airway epithelial cells. Several investigators have reported that, in CF airway fluids, elevated NaCl concentrations may also contribute to the diseased state by inhibiting the bactericidal properties of airway fluid. Because many proinflammatory cytokines are transcriptionally regulated by the NF-kappa B, we investigated whether an elevated extracellular NaCl content in airway fluids significantly impaired the regulation of the NF-kappa B/I kappa B alpha complex and the chemokine IL-8 production in primary non-CP and CF human bronchial gland epithelial cells. Exposure of non-CF gland cells to hypotonic (85 mM) NaCl solution, compared with isotonic (115 mM) NaCl and hypertonic (170 mM) NaCl solutions, resulted in a significant decrease in IL-8 production that was paralleled hy a strong inhibition of activated NF-kappa B associated with an increased cytosolic expression of I kappa B alpha and a decrease in the I kappa B kinase alpha protein level, In CF gland cells, we demonstrated that, compared with the high IL-8 in an hypertonic solution, the release of IL-8 was significantly reduced 2-fold in an isotonic solution and 5-fold in a hypotonic solution. Strikingly, exposure of CF bronchial gland cells to either hypotonic or isotonic milieu did not result in a marked inhibition of the activated NF-kappa B/I kappa B alpha system. This is the first demonstration that primary human CF bronchial gland cells exhibit abnormally high IL-8 production through constitutively activated NF-kappa B and high I kappa B kinase alpha level, whatever the hypo-, iso-, and hypertonic NaCl milieu.
引用
收藏
页码:3377 / 3384
页数:8
相关论文
共 32 条
[1]   NF-kappa B: Ten years after [J].
Baeuerle, PA ;
Baltimore, D .
CELL, 1996, 87 (01) :13-20
[2]   CENTRAL OF I-KAPPA-B-ALPHA PROTEOLYSIS BY SITE-SPECIFIC, SIGNAL-INDUCED PHOSPHORYLATION [J].
BROWN, K ;
GERSTBERGER, S ;
CARLSON, L ;
FRANZOSO, G ;
SIEBENLIST, U .
SCIENCE, 1995, 267 (5203) :1485-1488
[3]   A cytokine-responsive I kappa B kinase that activates the transcription factor NF-kappa B [J].
DiDonato, JA ;
Hayakawa, M ;
Rothwarf, DM ;
Zandi, E ;
Karin, M .
NATURE, 1997, 388 (6642) :548-554
[4]   Activation of NF-κB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells [J].
DiMango, E ;
Ratner, AJ ;
Bryan, R ;
Tabibi, S ;
Prince, A .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (11) :2598-2605
[5]   SUBMUCOSAL GLANDS ARE THE PREDOMINANT SITE OF CFTR EXPRESSION IN THE HUMAN BRONCHUS [J].
ENGELHARDT, JF ;
YANKASKAS, JR ;
ERNST, SA ;
YANG, YP ;
MARINO, CR ;
BOUCHER, RC ;
COHN, JA ;
WILSON, JM .
NATURE GENETICS, 1992, 2 (03) :240-248
[6]   INCREASED BRONCHIAL CHLORIDE CONCENTRATION IN CYSTIC-FIBROSIS [J].
GILLJAM, H ;
ELLIN, A ;
STRANDVIK, B .
SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION, 1989, 49 (02) :121-124
[7]   Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis [J].
Goldman, MJ ;
Anderson, GM ;
Stolzenberg, ED ;
Kari, UP ;
Zasloff, M ;
Wilson, JM .
CELL, 1997, 88 (04) :553-560
[8]   Cystic fibrosis and the salt controversy [J].
Guggino, WB .
CELL, 1999, 96 (05) :607-610
[9]   GLANDULAR-LIKE MORPHOGENESIS AND SECRETORY ACTIVITY OF HUMAN TRACHEAL GLAND-CELLS IN A 3-DIMENSIONAL COLLAGEN GEL MATRIX [J].
JACQUOT, J ;
SPILMONT, C ;
BURLET, H ;
FUCHEY, C ;
BUISSON, AC ;
TOURNIER, JM ;
GAILLARD, D ;
PUCHELLE, E .
JOURNAL OF CELLULAR PHYSIOLOGY, 1994, 161 (03) :407-418
[10]  
JACQUOT J, 1993, EUR RESPIR J, V6, P169