CYTOKINE AND ADHESION MOLECULE EXPRESSION IN HUMAN MONOCYTES AND ENDOTHELIAL-CELLS STIMULATED WITH BACTERIAL HEAT-SHOCK PROTEINS

Bacterial heat shock proteins (HSPs) from Escherichia coli (GroFS, Gro EL, and DNAk) were tested for their ability to induce by themselves th e expression and release of interleukin-6 (IL-6), tumor necrosis facto r alpha (TNF-alpha), and granulocyte-monocyte colony-stimulating facto r (GM-CSF) by human monocytes and GM-CSF, IL-6, E-selectin, intercellu lar adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule- 1 (VCAM-1) by human umbilical vein endothelial cells (HUVEC). Our stud y demonstrated that treatment of monocytes with DNAk increased IL-6, T NF-alpha, and GM-CSF release in a dose-dependent manner. The same effe ct was elicited by GroEL but at a lower rate. Treatment of HUVEC cultu res with DNAk and GroEL also increased GM-CSF, IL-6, E-selectin, ICAM- 1, and VCAM-1 release in a dose-dependent fashion. In any case, the gr eatest release was obtained by using DNAk and GroEL at a concentration of 1 mu g/ml. DNAk and GroEL were also able to up-regulate the surfac e expression of E-selectin, ICAM-1, and VCAM-1. As detected by reverse transcription-PCR analysis, DNAk and GroEL also increased the steady- state levels of cytokines and adhesion molecules in human monocytes an d endothelial cells. In our study GroES showed a significant activity only on the release, surface expression, and mRNA transcription of E-s electin, Adhesion molecule expression seems to be a direct effect of H SPs and not via cytokines. Furthermore, these effects are due to HSPs properties because they are inhibited by specific monoclonal antibodie s. These findings support the potential role of HSPs in modulating cel l interactions during immunological and inflammatory responses.