Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability

Abstract

Dokladny, Karol, Pope L. Moseley, and Thomas Y. Ma. Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability. Am J Physiol Gastrointest Liver Physiol 290: G204 -G212, 2006; doi:10.1152/ajpgi.00401.2005.-The effects of physiologically relevant increase in temperature (37-41°C) on intestinal epithelial tight junction (TJ) barrier have not been previously studied. Additionally, the role of heat-shock proteins (HSPs) in the regulation of intestinal TJ barrier during heat stress remains unknown. Because heat-induced disturbance of intestinal TJ barrier could lead to endotoxemia and bacterial translocation during physiological thermal stress, the purpose of this study was to investigate the effects of modest, physiologically relevant increases in temperature (37-41°C) on intestinal epithelial TJ barrier and to examine the protective role of HSPs on intestinal TJ barrier. Filtergrown Caco-2 intestinal epithelial cells were used as an in vitro intestinal epithelial model system to assess the effects of heat exposure on intestinal TJ barrier. Exposure of filter-grown Caco-2 monolayers to modest increases in temperatures (37-41°C) resulted in a significant time-and temperature-dependent increases in Caco-2 TJ permeability. Exposure to modest heat (39 or 41°C) resulted in rapid and sustained increases in HSP expression; and inhibition of HSP expression produced a marked increase in heat-induced increase in Caco-2 TJ permeability (P Ͻ 0.001). Heat exposure (41°C) resulted in a compensatory increase in Caco-2 occludin protein expression and an increase in junctional localization. Inhibition of HSP expression prevented the compensatory upregulation of occludin protein expression and produced a marked disruption in junctional localization of occludin protein during heat stress. In conclusion, our findings demonstrate for the first time that a modest, physiologically relevant increase in temperature causes an increase in intestinal epithelial TJ permeability. Our data also show that HSPs play an important protective role in preventing the heat-induced disruption of intestinal TJ barrier and suggest that HSP mediated upregulation of occludin expression may be an important mechanism involved in the maintenance of intestinal epithelial TJ barrier function during heat stress.

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

“…Increased rates of organ-specific cell death are considered to be involved in the pathophysiology of MODS in a variety of systemic disorders, including heatstroke (35,52), contributing to the breakdown of intestinal barrier function observed during endotoxemia (13,15,39,66,80,85). Increased physiological levels of inflammatory stimuli can promote an increase in cellular apoptosis (52,63), which is supported by the finding that TNF receptor shares intracellular signaling domains with FAS/CD95, a crucial receptor involved with apoptotic signaling (48).…”

Risk of tuberculosis in a large sample of patients with coeliac disease - a nationwide cohort study

“…34 Even at physiologically relevant temperature increases, the permeability of intestinal epithelium is increased. 35 We cannot rule out that some individuals with TB were identified as part of the investigations for CD. The highest risk estimates were seen in the first year after diagnosis even if the HR for TB remained statistically significant thereafter.…”

Heat shock response and autophagy—cooperation and control

“…[121][122][123] The primary function of these heat shock proteins is to fold nascent proteins and refold denatured proteins after cellular stress. 7,124,125 The heat shock proteins also modulate physiology of a single cell or whole organism by regulating signaling pathways, 126 cell survival, 127 tight junction permeability, [128][129][130] cytokine expression, 131 and protein degradation. 25,132 HSP70 is the most highly conserved member in the HSP family and has been studied in the response to acute exercise or exercise training in animals.…”