Increased expression of urokinase type plasminogen activator(u-PA), plasminogen activator inhibitor-1 (PAI-1), and collagenases in caco-2 cells infected by Salmonella typhimurium

Abstract

Salmonella penetrates the basement membrane of intestinal epithelial cells into deeper tissues, in which process extracellular matrix proteases should be required. Hypothesizing that the proteases might be provided by host cells, we investigated the changes of expression of urokinase type plasminogen activator(u-PA), plasminogen activator inhibitor-1(PAI-1), and collagenases in epithelial cells(Caco-2) infected with Salmonella typhimurium. The change of mRNA levels, amount of the enzyme secretion and functional activity were analyzed by Northern blot, ELISA, and Zymography. The mRNA level of u-PA was elevated by Salmonella infection itself without any exogenous transcription regulators. u-PA was actively secreted into the medium and was enzymatically active. The synthesis and secretion of PAI-1 was increased over time from 2hrs post infection(pi) to 8hrs pi. Zymographic assay revealed that the secretion of collagenases(type IV, type V and interstitial collagenase) were also increased. Taken together, S. typhimurium infection might induce accumulation of pericellular proteolytic activity and consequently degrade the extracellular matrix surrounding the infected cells. These in turn might enable Salmonella to invade into deeper tissues.