FIBRONECTIN MODULATES EXPRESSION OF INTERLEUKIN-1-BETA AND ITS RECEPTOR ANTAGONIST IN HUMAN MONONUCLEAR-CELLS

Identification of factors that regulate production of proinflammatory cytokines may provide insight into mechanisms governing lung inflammat ion. One potential regulatory factor highly expressed in inflamed tiss ues is fibronectin (FN). To determine the potential effects of FN on i nterleukin (IL)-1 beta production, we exposed human peripheral blood m ononuclear cells to soluble FN. This treatment resulted in the accumul ation of IL-1 beta mRNA and enhancement of IL-1 beta protein synthesis and secretion. This effect was dose dependent and appeared to be medi ated by the integrin alpha(5) beta(1). Treatment with FN also increase d production of IL-1 receptor antagonist (IL-1ra), a naturally occurri ng inhibitor of IL-1 function. However, the stimulatory effect of FN o n IL-1ra production was abolished by costimulation with type I collage n. We conclude that the increased deposition of FN in injured tissues may enhance the expression of IL-1 beta mRNA and augment the productio n and release of IL-1 beta protein by mononuclear cells. Differential expression of IL-1 beta and IL-1ra resulting in a high IL-1 beta-to-IL -1ra ratio in response to mixed matrices containing FN and type I coll agen may be an important regulatory point in inflammation.