&cestchinlong;The heat shock response and cytoprotection of the intestinal epithelium

Abstract

Following heat stress, the mammalian intestinal epithelial cells respond by producing heat shock proteins that confer protection under stressful conditions, which would otherwise lead to cell damage or death. Some of the noxious processes against which the heat shock response protects cells include heat stress, infection, and inflammation. The mechanisms of heat shock response-induced cytoprotection involve inhibition of proinflammatory cytokine production and induction of cellular proliferation for restitution of the damaged epithelium. This can mean selective interference of pathways, such as nuclear factor kappa B (NF-kappaB) and mitogen-activated protein kinase (MAPK), that mediate cytokine production and growth responses. Insight into elucidating the exact protective mechanisms could have therapeutic significance in treating intestinal inflammations and in aiding maintenance of intestinal integrity. Herein we review findings on heat shock response-induced intestinal epithelial protection involving regulation of NF-kappaB and MAPK cytokine production.

Inhibition of Salmonella-induced IL-8 synthesis and expression of Hsp70 in enterocyte-like Caco-2 cells after exposure to non-starter lactobacilli

“…This response is specific to the bacteria and their SCS since the MRS broth or variations in pH could not induce the Hsp70 expression. Because the production of Hsp70 is a protective response (Malago et al, 2002;Ovelgönne et al, 2000), we suggest that one mechanism for the beneficial attributes of the non-starter lactobacilli is the ability to induce the expression of Hsp70 by the bacteria and their antimicrobial products. The induced Hsp70 could function in the stabilisation of the cytoskeleton of intestinal epithelial cells after being distorted during adhesion and invasion by Salmonella (Jepson et al, 1995(Jepson et al, , 1996.…”

“…Further, when administered intravenously, lactobacilli cultivation products induce the expression of a putative protective protein (Hsp70) in the rat heart that subsequently protects the heart against ischaemia and reperfusion tachyarrhythmia (Oxman et al, 2000). Since heat shock proteins suppress the synthesis of inflammatory cytokines like IL-8 (Malago et al, 2002) and lactobacilli induce these proteins in the rat heart, it is reasonable to suggest that lactobacilli also exert a beneficial effect upon the gut following oral uptake.…”

“…Although some lactobacilli inhibit IL-8 production by intestinal epithelial cells and some are implicated in the treatment and prevention of such intestinal diseases Gionchetti et al, 2000), the direct link between suppression of IL-8 and alleviation of these diseases imparted by lactobacilli has not been established. Furthermore, the capacity of lactobacilli to induce Hsp70 that is known to inhibit IL-8 production by intestinal epithelial cells (Oxman et al, 2000;Malago et al, 2002), suggests a positive correlation between induction of Hsps, inhibition of IL-8 and improvement of intestinal disorders in the gut inhabited by lactobacilli. It is therefore compelling to hypothesize that part of the mechanism imparted by lactobacilli to the welfare of the intestinal epithelium involves regulation of IL-8 production either direct or indirect via induction of Hsp synthesis.…”

Sodium arsenite reduces severity of dextran sulfate sodium-induced ulcerative colitis in rats

“…This chemoattractant is produced following activation of the transcription factor, nuclear factor kappa B (NF-κB) (Malago et al, 2002). DSS can activate this factor and could in turn lead to synthesis and secretion of IL-8 (Marrero et al, 2000).…”

“…Since polymorphonuclear neutrophil infiltration is the primary and central lesion of colitis and is usually followed by loss of the epithelium, loss of goblet cells and crypt damage (Iba et al, 2003), it follows that the observed SA protection against colitis in this study could be mediated via its ability to inhibit the polymorphonuclear neutrophil infiltration and the subsequent pathology. SA is well known to mediate most of its effects via activation of the heat shock response that, in turn, suppresses the inflammatory response (Malago et al, 2002). The dose of SA used in this study (10 mg/kg, intraperitoneally, every 48 h) had a broad safety margin, as none of the rats died or showed abnormal behavior due to SA.…”