Graves K L, Roman J
Department of Medicine, Atlanta Veterans Affairs Medical Center, Emory University School of Medicine, Georgia 30033, USA.
Am J Physiol. 1996 Jul;271(1 Pt 1):L61-9. doi: 10.1152/ajplung.1996.271.1.L61.
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 interleukin (IL)-1 beta production, we exposed human peripheral blood mononuclear cells to soluble FN. This treatment resulted in the accumulation of IL-1 beta mRNA and enhancement of IL-1 beta protein synthesis and secretion. This effect was dose dependent and appeared to be mediated by the integrin alpha 5 beta 1. 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 costimulation with type I collagen. We conclude that the increased deposition of FN in injured tissues may enhance the expression of IL-1 beta mRNA and augment the production 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 collagen may be an important regulatory point in inflammation.
确定调节促炎细胞因子产生的因素可能有助于深入了解肺部炎症的调控机制。在炎症组织中高度表达的一种潜在调节因子是纤连蛋白（FN）。为了确定FN对白细胞介素（IL）-1β产生的潜在影响，我们将人外周血单核细胞暴露于可溶性FN中。这种处理导致IL-1β mRNA的积累以及IL-1β蛋白合成和分泌的增强。这种效应呈剂量依赖性，并且似乎是由整合素α5β1介导的。用FN处理还增加了IL-1受体拮抗剂（IL-1ra）的产生，IL-1ra是一种天然存在的IL-1功能抑制剂。然而，FN对IL-1ra产生的刺激作用被I型胶原的共刺激所消除。我们得出结论，FN在受损组织中沉积的增加可能会增强IL-1β mRNA的表达，并增加单核细胞产生和释放IL-1β蛋白。在含有FN和I型胶原的混合基质作用下，IL-1β和IL-1ra的差异表达导致高IL-1β/IL-1ra比值，这可能是炎症中的一个重要调控点。
