Pulmonary fibroblasts actively secrete PAI-1 at injured sites. KiF fibroblasts with the deletion allele of the PAI-1 promoter gene produced and secreted larger amounts of PAI-1 than WI-38 fibroblasts with the insertion allele. The effects of dexamethasone on PAI-1 expression after stimulation with TNFα were examined using these two human lung fibroblast lines. Dexamethasone initially reduced TNFα-induced NF-κB translocation, PAI-1 mRNA expression and PAI-1 secretion. The effects in KiF appeared earlier than in WI-38. However, longer treatment with dexamethasone eventually led to larger PAI-1 secretion than that observed in TNFa-unstimulated cells. These results suggest that the polymorphism of the PAI-1 promoter gene regulates not only PAI-1 production but also the response to dexamethasone.
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