Sustained expression of cytoprotective
intestinal epithelial heat shock proteins (Hsps), particularly
Hsp27, depends on stimuli
derived from
bacterial flora. In this study, we examined the role of the
bacterial chemotactic peptide fMLP in stimulating
colonic epithelial Hsp expression at concentrations encountered in a physiological milieu. Treatment of the
polarized human
intestinal epithelial cell line Caco2bbe with physiological concentrations of fMLP (10-100 nM) induced expression of
Hsp27, but not
Hsp72, in a time- and concentration-dependent manner. Induction of
Hsp27 by fMLP was specific since the fMLP analogs MRP and MLP were not effective.
Hsp27 induction by fMLP was blocked by the fMLP-receptor antagonist BOC-FLFLF and was blocked when the
dipeptide transporter PepT1, an entry pathway for fMLP, was silenced. fMLP activated both the p38 and
ERK1/2
MAP kinase pathways in Caco2bbe cells, but not the SAPK/
JNK pathway. The p38 inhibitor SB203580, but not the MEK-1 inhibitor PD98059, blocked
Hsp27 induction by fMLP. fMLP treatment inhibited
actin depolymerization and decreased transepithelial resistance caused by the
oxidant monochloramine, and this inhibition was reversed by silencing
Hsp27 expression. fMLP pretreatment also inhibited
activation of
proinflammatory transcription factor NF-kappaB by
TNF-alpha in Caco2bbe cells, reducing induction of
NF-kappaB target genes by
TNF-alpha both in human
intestinal biopsies and Caco2bbe cells. In conclusion, fMLP may contribute to the maintenance of
intestinal homeostasis by mediating physiological expression of
Hsp27, enhancing cellular protection, and negatively regulating the
inflammatory response.
