LIPOPOLYSACCHARIDE INDUCES EXPRESSION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, INTERLEUKIN-8, AND INTERLEUKIN-6 IN HUMAN NASAL, BUT NOT LUNG, FIBROBLASTS - EVIDENCE FOR HETEROGENEITY WITHIN THE RESPIRATORY-TRACT

被引:74
作者
XING, Z [1 ]
JORDANA, M [1 ]
BRACIAK, T [1 ]
OHTOSHI, T [1 ]
GAULDIE, J [1 ]
机构
[1] MCMASTER UNIV, CHEDOKE MCMASTER MED CTR, HLTH SCI CTR, DEPT PATHOL, HAMILTON L8N 3Z5, ONTARIO, CANADA
关键词
D O I
10.1165/ajrcmb/9.3.255
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Fibroblasts play an indirect augmenting effector role in the inflammatory response by releasing growth and differentiation factors and other inflammatory mediators after activation by inflammatory cytokines such as interleukin (IL)-1, but whether direct activation occurs by exogenous agents such as endotoxin (lipopolysaccharide, LPS) remains controversial. Using a number of primary human airways tissue-derived fibroblast lines, we demonstrate that in contrast to IL-1alpha, LPS significantly induced gene expression and production of granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-8, and IL-6 only in nasal but not bronchial or lung tissue-derived fibroblasts. Enhanced expression was dose- and time-dependent, and the minimal stimulatory dose was 10 ng LPS/ml. Polymyxin B entirely abrogated increased cytokine expression by LPS. Actinomycin D treatment largely inhibited expression, and LPS markedly increased an IL-6 gene promoter-driven luciferase reporter response in transfected nasal fibroblasts, suggesting enhanced expression may involve transcriptional regulation. Secondary protein or IL-1 synthesis requirement seemed unlikely since cycloheximide superinduced LPS-stimulated cytokine expression and anti-IL-1alpha/beta antibodies failed to abrogate the response. Thus our data show that GM-CSF, IL-8, and IL-6 are directly inducible in nasal fibroblasts by LPS, and establish heterogeneous responsiveness to LPS by different fibroblast populations in the airways.
引用
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页码:255 / 263
页数:9
相关论文
共 58 条
[1]  
Aarden L, 1985, LYMPHOKINES, V10, P175
[2]   ROLE OF LYMPHOTOXIN IN EXPRESSION OF INTERLEUKIN-6 IN HUMAN-FIBROBLASTS - STIMULATION AND REGULATION [J].
AKASHI, M ;
LOUSSARARIAN, AH ;
ADELMAN, DC ;
SAITO, M ;
KOEFFLER, HP .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (01) :121-129
[3]   ENDOTOXIN STIMULATES PLATELET-DERIVED GROWTH-FACTOR PRODUCTION FROM CULTURED HUMAN PULMONARY ENDOTHELIAL-CELLS [J].
ALBELDA, SM ;
ELIAS, JA ;
LEVINE, EM ;
KERN, JA .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (02) :L65-L70
[4]  
BAFFET G, 1991, MOL BIOL MED, V8, P141
[5]   DIFFERENTIAL PRODUCTION OF TUMOR NECROSIS FACTOR, MACROPHAGE COLONY STIMULATING FACTOR, AND INTERLEUKIN-1 BY HUMAN ALVEOLAR MACROPHAGES [J].
BECKER, S ;
DEVLIN, RB ;
HASKILL, JS .
JOURNAL OF LEUKOCYTE BIOLOGY, 1989, 45 (04) :353-361
[6]  
CAVAILLON J-M, 1990, Cytokine, V2, P313, DOI 10.1016/1043-4666(90)90061-W
[7]  
CHODAKEWITZ JA, 1990, J IMMUNOL, V144, P2190
[8]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[9]   PROMOTION OF EOSINOPHIL SURVIVAL BY HUMAN BRONCHIAL EPITHELIAL-CELLS AND ITS MODULATION BY STEROIDS [J].
COX, G ;
OHTOSHI, T ;
VANCHERI, C ;
DENBURG, JA ;
DOLOVICH, J ;
GAULDIE, J ;
JORDANA, M .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1991, 4 (06) :525-531
[10]   CYTOKINE NETWORKS IN THE REGULATION OF INFLAMMATION AND FIBROSIS IN THE LUNG [J].
ELIAS, JA ;
FREUNDLICH, B ;
KERN, JA ;
ROSENBLOOM, J .
CHEST, 1990, 97 (06) :1439-1445