Pulmonary fibroblast expression of interleukin-8: a model for alveolar macrophage-derived cytokine networking.
The pulmonary fibroblast's (PF) unique location allows it to communicate in a bidirectional fashion between the vascular compartment and alveolar airspace, placing it in a strategic position for the elicitation of inflammatory leukocytes into the lung. In this study, we demonstrate that PF may contribute to pulmonary inflammation through the production of a potent neutrophil chemotactic factor, interleukin (IL)-8. PF-derived IL-8 expression was dependent upon stimulation by either tumor necrosis factor (TNF) or IL-1 but not lipopolysaccharide (LPS). Both TNF and IL-1 stimulation of PF resulted in a time- and dose-dependent expression of steady-state levels of mRNA, antigen, and specific chemotactic activity consistent with IL-8. Because it was apparent that cytokine networking may exist in the lung between alveolar macrophage (AM)-derived cytokines and the production of PF-derived IL-8, we next examined an in vitro model of cellular communication within the lung. We determined that LPS-stimulated AM-conditioned media induced significant levels of PF-derived IL-8 mRNA, which was inhibited by preincubation with specific neutralizing TNF and IL-1 beta antibodies. Furthermore, when AM were directly co-cultured with PF and stimulated with LPS, the kinetic analysis of PF-derived antigenic expression of IL-8 was shifted toward the right. This suggested that PF-derived IL-8 expression in co-culture was first dependent upon activation of the AM by LPS and subsequent elaboration of macrophage inflammatory mediators. These data provide evidence that cytokine networking between AM and PF may be operative in the lung, culminating in the generation of IL-8 and elicitation of inflammatory leukocytes.
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
M W
MW
Rolfe
S L
SL
Kunkel
T J
TJ
Standiford
S W
SW
Chensue
R M
RM
Allen
H L
HL
Evanoff
S H
SH
Phan
R M
RM
Strieter
D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D002450:Cell Communication; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007700:Kinetics; D008070:Lipopolysaccharides; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D015345:Oligonucleotide Probes
D000906:Antibodies; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D015345:Oligonucleotide Probes