Induction of heat shock gene expression in colonic epithelial cells after incubation with Escherichia coli or endotoxin

Abstract
Objective The universal cellular response to stress is the expression of a family of genes known as heat shock or stress proteins. We investigated whether bacteria or bacterial products (endotoxin) can induce heat shock protein expression in human enterocytes. Design Controlled, in vitro study. Setting Cell culture laboratory. Subjects Human Caco-2 enterocyte cell line. Measurements and Main Results Incubation of confluent monolayers of Caco-2 cells with Escherichia coli C25 (1 times 109 bacteria/mL) for 1 hr at 37 degrees C was found to induce the expression of the 72-kilodalton molecular weight heat shock protein gene (heat shock protein-72), the major inducible form of the 70-kilodalton molecular weight heat shock protein family of stress proteins, as detected by Western blot analysis. The level of heat shock protein-72 induction after incubation with E. coli was similar to the response of Caco-2 cells to heat shock at 43 degrees C for 1 hr. The induction of heat shock protein-72 gene expression by E. coli was not purely due to the process of phagocytosis, since incubation of Caco-2 cells with latex beads (1 micro meter) failed to induce heat shock gene expression. To elucidate the possible mechanism of heat shock protein-72 induction mediated by bacteria, Caco-2 cells were incubated with E. coli endotoxin (200 micro gram/mL) for 1 hr at 37 degrees C. Such treatment was also found to induce the synthesis of heat shock protein-72. Conclusions These results demonstrate that bacteria and/or bacterial products induce the heat shock gene expression in Caco-2 cells. Since intestinal epithelial cells are constantly in contact with bacteria and bacterial products, we speculate that the heat shock gene expression may be part of the natural mechanism of protection for these cells in the potentially harmful environment that may be present in the intestinal tract. (Crit Care Med 1995; 23:1371-1376)