Abstract
AbstractProduction of hematopoietic growth factors by endothelial cells plays a pivotal role during inflammatory processes. Stem cell factor (SCF) is known to be expressed constitu-tively in endothelial cells. To investigate the regulation of this cytokine expression by inflammatory stimuli, we cocul-tured human umbilical vein endothelial cells (HUVEC) with various gram-negative bacterial strains [Escherichia coli. Yersinia enterocolitica. Chlamydia trachomatis, and Neisseria meningitidis, respectively). Experiments were performed with bacterial concentrations ranging from 102 to 107 bacteria/mL for 3 hours. SCF-specific mRNA expression was studied using Northern blot analysis. Stimulation with the enteropathogenic bacterial strains Y enterocolitica and Ecoli resulted in a significant concentration-dependent increase of SCF mRNA expression. Similar results were obtained in coculture experiments with N meningitidis. As shown in experiments with E coli, the accumulation of SCF transcripts was also time-dependent. In contrast, coculture of HUVEC with the intracellular gram-negative strain C trachomatis had no effect on SCF mRNA expression. To elucidate the role of the gram-negative bacterial cell wall components, we stimulated HUVEC with bacterial lipopolysaccharide (LPS). LPS induced a maximal SCF mRNA accumulation within 2 hours followed by decrease of SCF-specific transcripts to the basal level after 24 hours. In addition, we exposed HUVEC to the classical inflammatory cytokine interleukin-1α (IL-1α). Kinetic experiments showed a similar pattern of regulation with an increase of SCF mRNA within 2 hours, persisting up to 12 hours, and a decrease to basal transcription after 24 hours. From these data, we conclude that SCF expression is regulated by inflammatory stimuli, such as IL-1α and bacterial pathogens, suggesting an important role of SCF during inflammation.
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