Fibronectin modulates the expression of interleukin-1b and its
receptor antagonist in human mononuclear cells.
Graves, Karen L., and Jesse Roman.
Department of Medicine, Atlanta Veterans Affairs Medical Center,
Emory University School of Medicine, Atlanta, Georgia 30033
APStracts 3:0040L, 1996.
Identification of factors that regulate production of proinflammatory
cytokines may provide insight into mechanisms governing lung
inflammation. One potential regulatory factor highly expressed in
inflamed tissues is fibronectin (FN). To determine the potential
effects of FN on IL-1b production, we exposed human peripheral blood
mononuclear cells to soluble FN. This treatment resulted in the
accumulation of IL-1b mRNA and enhancement of IL-1b protein synthesis
and secretion. This effect was dose-dependent and appeared to be
mediated by the integrin a5b1. Treatment with FN also increased
production of IL-1 receptor antagonist (IL-1ra), a naturally
occurring inhibitor of IL-1 function. However, the stimulatory effect
of FN on IL-1ra production was abolished by co-stimulation with type
I collagen. We conclude that the increased deposition of FN in
injured tissues may enhance the expression of IL-1b mRNA and augment
the production and release of IL-1b protein by mononuclear cells.
Differential expression of IL-1b and IL-1ra resulting in a high IL
-1b/IL-1ra ratio in response to mixed matrices containing FN and type
I collagen may be an important regulatory point in inflammation.
Received 22 September 1995; accepted in final form 28 December
1995.
APS Manuscript Number L282-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96