Heat shock response reduces intestinal permeability in septic mice: potential role of interleukin-10

2002 ◽  
Vol 282 (3) ◽  
pp. R669-R676 ◽  
Author(s):  
Quan Wang ◽  
Per-Olof Hasselgren
Keyword(s):  
Heat Shock ◽  
Intestinal Permeability ◽  
Heat Shock Response ◽  
Sodium Arsenite ◽  
Cecal Ligation ◽  
Interleukin 10 ◽  
Sham Operation ◽  
Protective Effects ◽  
Mucosal Permeability ◽  
Shock Response

Sepsis and other critical illnesses are associated with increased permeability of the intestinal mucosa. Loss of mucosal integrity may lead to multiple organ failure in these conditions. We tested the hypothesis that induction of the heat shock response reduces sepsis-induced increase in intestinal permeability. The heat shock response was induced in mice by intraperitoneal injection of 10 mg/kg sodium arsenite. Two hours later, at which time mucosal heat shock protein 72 levels were increased, sepsis was induced by cecal ligation and puncture (CLP) or sham operation was performed. Sixteen hours after sham operation or CLP, intestinal permeability was determined by measuring the appearance in blood of 4.4-kDa fluorescein isothiocyanate-conjugated dextran and 40-kDa horseradish peroxidase administered by gavage. Sepsis resulted in increased mucosal permeability for both markers, and this effect of sepsis was substantially reduced in mice treated with sodium arsenite. Plasma levels of the anti-inflammatory cytokine interleukin (IL)-10 were increased in septic mice pretreated with sodium arsenite, and the protective effect of sodium arsenite on intestinal permeability in septic mice was reversed by treatment with anti-IL-10 antibody. The present results suggest that sepsis-induced increase in mucosal permeability can be reduced by the heat shock response and that increased IL-10 levels may be involved in the protective effects of the heat shock response.

scholarly journals Dephosphorylation of S6 and expression of the heat shock response in Drosophila melanogaster.

1983 ◽  
Vol 3 (11) ◽  
pp. 2017-2027 ◽  
Author(s):  
A S Olsen ◽  
D F Triemer ◽  
M M Sanders
Keyword(s):  
Protein Synthesis ◽  
Drosophila Melanogaster ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Sodium Arsenite ◽  
Large Fraction ◽  
Ribosomal Subunit ◽  
Liver Protein ◽  
Chemical Inducers ◽  
Shock Response

A basic ribosomal phosphoprotein of 30,000 molecular weight was rapidly dephosphorylated in cultured Drosophila melanogaster cells heat shocked at 37 degrees C. The protein was associated with the 40S ribosomal subunit and had an electrophoretic mobility similar to that of purified rat liver protein S6 on basic two-dimensional polyacrylamide gels as well as a similar partial proteolysis peptide map. In logarithmically growing cultures, this D. melanogaster S6 protein appeared to have a single phosphorylated species consisting of 30 to 40% of the total cellular S6. Thus, the nearly complete dephosphorylation of this protein observed in heat shock involves a large fraction of the cellular S6. The significance of this dephosphorylation in the expression of the heat shock response was investigated by examining the phosphorylation status of S6 in recovery from heat shock and in response to chemical inducers of the heat shock response. During recovery from a 30-min heat shock, the recovery of normal protein synthesis was almost complete in 2 to 4 hr, whereas there was no significant rephosphorylation of S6 for 8 h. Two chemical inducers of the heat shock response, canavanine and sodium arsenite, induced the synthesis of heat shock proteins in D. melanogaster cells. Sodium arsenite also caused an inhibition of normal protein synthesis similar to that observed in heat shock. Neither agent, however, caused significant dephosphorylation of S6. These results suggest that the dephosphorylation of S6, although invariably observed in heat-shocked cells, may in some cases be dissociated from both the induction of heat shock protein synthesis and the turnoff of normal protein synthesis which occur in a heat shock response.

scholarly journals Intestinal permeability is reduced and IL-10 levels are increased in septic IL-6 knockout mice

2001 ◽  
Vol 281 (3) ◽  
pp. R1013-R1023 ◽  
Author(s):  
Quan Wang ◽  
Cheng Hui Fang ◽  
Per-Olof Hasselgren
Keyword(s):  
Intestinal Permeability ◽  
Cecal Ligation ◽  
Fluorescein Isothiocyanate ◽  
Sham Operation ◽  
Cecal Ligation And Puncture ◽  
Wild Type ◽  
Mucosal Permeability ◽  
Ussing Chambers ◽  
Intestinal Segments

Sepsis is associated with increased intestinal permeability, but mediators and mechanisms are not fully understood. We examined the role of interleukin (IL)-6 and IL-10 in sepsis-induced increase in intestinal permeability. Intestinal permeability was measured in IL-6 knockout (IL-6 −/−) and wild-type (IL-6 +/+) mice 16 h after induction of sepsis by cecal ligation and puncture or sham operation. In other experiments, mice or intestinal segments incubated in Ussing chambers were treated with IL-6 or IL-10. Intestinal permeability was assessed by determining the transmucosal transport of the 4.4-kDa marker fluorescein isothiocyanate conjugated dextran and the 40-kDa horseradish peroxidase. Intestinal permeability for both markers was increased in septic IL-6 +/+ mice but not in septic IL-6 −/− mice. Treatment of nonseptic mice or of intestinal segments in Ussing chambers with IL-6 did not influence intestinal permeability. Plasma IL-10 levels were increased in septic IL-6 −/− mice, and treatment of septic mice with IL-10 resulted in reduced intestinal permeability. Increased intestinal permeability during sepsis may be regulated by an interaction between IL-6 and IL-10. Treatment with IL-10 may prevent the increase in mucosal permeability during sepsis.

Expression of iNOS in cultured rat pulmonary artery smooth muscle cells is inhibited by the heat shock response

1995 ◽  
Vol 269 (6) ◽  
pp. L843-L848 ◽  
Author(s):  
H. R. Wong ◽  
J. D. Finder ◽  
K. Wasserloos ◽  
B. R. Pitt
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Sodium Arsenite ◽  
Dependent Manner ◽  
Inos Gene ◽  
Shock Response ◽  
Pulmonary Artery Smooth Muscle ◽  
Inos Gene Expression

The heat shock response is a highly conserved stress response known to alter patterns of gene expression in many cell types. We hypothesized that interleukin-1 beta (IL-1 beta)-mediated inducible nitric oxide synthase (iNOS) gene expression would be inhibited after induction of the heat shock response in cultured rat pulmonary artery smooth muscle cells (RPASMC). Exposure of RPASMC to sodium arsenite or heat led to expression of heat shock protein-70 (HSP-70) in a time- and concentration-dependent manner. Prior induction of the heat shock response inhibited IL-1 beta-mediated iNOS gene expression in a time- and dose-dependent manner. The inhibitory effects were not due to cytotoxicity, since cell viability was not affected by either sodium arsenite, heat, IL-1 beta, or their combination. Transcriptional analysis via transient transfection of the murine macrophage iNOS promoter [-1592 and -367 base pairs (bp)], upstream from the reporter gene luciferase, revealed that the heat shock response did not affect IL-1 beta-mediated promoter activation, as measured by luciferase activity. We conclude that induction of the heat shock response inhibits IL-1 beta-mediated iNOS gene expression in cultured RPASMC.

Induction of human endothelial cell apoptosis requires both heat shock and oxidative stress responses

1997 ◽  
Vol 272 (5) ◽  
pp. C1543-C1551 ◽  
Author(s):  
J. H. Wang ◽  
H. P. Redmond ◽  
R. W. Watson ◽  
D. Bouchier-Hayes
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cell ◽  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Sodium Arsenite ◽  
Oxidative Stress Response ◽  
Tnf Alpha ◽  
Shock Response ◽  
Hsp72 Expression

Endothelial cell (EC) death may play an important role in the development of increased vascular permeability and capillary leak syndrome during systemic inflammatory response syndrome. However, the mode of EC death and the mechanisms involved remain unclear. In this study we employed the proinflammatory mediators lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha), the chemical reagent sodium arsenite, and heat shock to trigger the stress gene responses. Human ECs were used as surrogates of the microvasculature to test the hypothesis that the induction of the heat shock response and the oxidative stress response might combine to induce apoptosis rather than necrosis in human ECs. Sodium arsenite at 80-320 microM, which induced heat shock protein 72 (HSP72) expression and reactive oxygen intermediate (ROI) generation in ECs, resulted in EC apoptosis. TNF-alpha alone (5-75 ng/ml) increased EC ROI generation but did not induce EC apoptosis. Heat shock alone (42 degrees C, 45 min) or sodium arsenite (40 microM) alone, each of which induced HSP72 expression, did not result in EC apoptosis. However, the combination of TNF-alpha with heat shock or 40 microM sodium arsenite led to EC apoptosis as HSP72 expression and ROI were induced. Furthermore, sodium arsenite (80 microM) in the presence of antioxidants failed to induce EC apoptosis. Apoptotic ECs also exhibited functional disturbances as represented by the depression of intercellular adhesion molecule-1 expression as well as the disruption of EC monolayer integrity. These results indicate that the simultaneous induction of a heat shock response and an oxidative stress response is responsible for human EC apoptosis.

Induction of a novel set of polypeptides by heat shock or sodium arsenite in cultured cells of rainbow trout, Salmo gairdnerii

1982 ◽  
Vol 60 (3) ◽  
pp. 347-355 ◽  
Author(s):  
R. K. Kothary ◽  
E. P. M. Candido
Keyword(s):  
Rainbow Trout ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Sodium Arsenite ◽  
Sodium Dodecyl ◽  
In Vitro Translation ◽  
Blue Staining ◽  
Transcriptional Level ◽  
Cultured Fibroblasts ◽  
Shock Response

The heat-shock response has been characterized in cultured fibroblasts of the rainbow trout, Salmo gairdnerii. The response has been elicited by two different stress situations; cells were either subjected to higher temperatures than normal (27 to 29 °C as opposed to 22 °C) or were incubated in medium containing sodium arsenite (15 to 100 μM final concentration). The response of the cells to these conditions is to synthesize a set of new polypeptides, the "heat-shock polypeptides" (hsps), that are not present or present in extremely low amounts in noninduced cells. Furthermore, during prolonged arsenite induction, the synthesis of normal cellular proteins is repressed. In trout fibroblasts, at least six hsps are detectable. These range from 30 000 to 87 000 in molecular weight and are referred to as hsp30, hsp32, hsp42, hsp62, hsp70, and hsp87. The hsp30 and hsp70 components are the most abundant and can be visualized by Coomassie blue staining of gels after prolonged induction. The heat-shock response is a reversible process in trout cells. Results of in vitro translation of mRNA from induced cells indicate that the control of hsp induction may be at the transcriptional level. Hsp70 from trout comigrates with the major hsp from Drosophila melanogaster on sodium dodecyl sulfate – polyacrylamide gels, suggesting that this protein may be highly conserved in evolution.

Dephosphorylation of S6 and expression of the heat shock response in Drosophila melanogaster

1983 ◽  
Vol 3 (11) ◽  
pp. 2017-2027
Author(s):  
A S Olsen ◽  
D F Triemer ◽  
M M Sanders
Keyword(s):  
Protein Synthesis ◽  
Drosophila Melanogaster ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Sodium Arsenite ◽  
Large Fraction ◽  
Ribosomal Subunit ◽  
Liver Protein ◽  
Chemical Inducers ◽  
Shock Response

A basic ribosomal phosphoprotein of 30,000 molecular weight was rapidly dephosphorylated in cultured Drosophila melanogaster cells heat shocked at 37 degrees C. The protein was associated with the 40S ribosomal subunit and had an electrophoretic mobility similar to that of purified rat liver protein S6 on basic two-dimensional polyacrylamide gels as well as a similar partial proteolysis peptide map. In logarithmically growing cultures, this D. melanogaster S6 protein appeared to have a single phosphorylated species consisting of 30 to 40% of the total cellular S6. Thus, the nearly complete dephosphorylation of this protein observed in heat shock involves a large fraction of the cellular S6. The significance of this dephosphorylation in the expression of the heat shock response was investigated by examining the phosphorylation status of S6 in recovery from heat shock and in response to chemical inducers of the heat shock response. During recovery from a 30-min heat shock, the recovery of normal protein synthesis was almost complete in 2 to 4 hr, whereas there was no significant rephosphorylation of S6 for 8 h. Two chemical inducers of the heat shock response, canavanine and sodium arsenite, induced the synthesis of heat shock proteins in D. melanogaster cells. Sodium arsenite also caused an inhibition of normal protein synthesis similar to that observed in heat shock. Neither agent, however, caused significant dephosphorylation of S6. These results suggest that the dephosphorylation of S6, although invariably observed in heat-shocked cells, may in some cases be dissociated from both the induction of heat shock protein synthesis and the turnoff of normal protein synthesis which occur in a heat shock response.

scholarly journals Heat-shock Response Increases Lung Injury Caused by Pseudomonas aeruginosa via an Interleukin-10-dependent Mechanism in Mice

2014 ◽  
Vol 120 (6) ◽  
pp. 1450-1462 ◽  
Author(s):  
Michel Carles ◽  
Brant M. Wagener ◽  
Mathieu Lafargue ◽  
Jérémie Roux ◽  
Karen Iles ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Heat Shock ◽  
Lung Injury ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Interleukin 10 ◽  
Bacterial Clearance ◽  
Epithelial Permeability ◽  
Heat Shock Protein 72 ◽  
Shock Response

Abstract Background: The heat-shock response (HSR) protects from insults, such as ischemia–reperfusion injury, by inhibiting signaling pathways activated by sterile inflammation. However, the mechanisms by which the HSR activation would modulate lung damage and host response to a bacterial lung infection remain unknown. Methods: HSR was activated with whole-body hyperthermia or by intraperitoneal geldanamycin in mice that had their lungs instilled with Pseudomonas aeruginosa 24 h later (at least six mice per experimental group). Four hours after instillation, lung endothelial and epithelial permeability, bacterial counts, protein levels in bronchoalveolar lavage fluid, and lung myeloperoxidase activity were measured. Mortality rate 24 h after P. aeruginosa instillation was recorded. The HSR effect on the release of interleukin-10 and killing of P. aeruginosa bacteria by a mouse alveolar macrophage cell line and on neutrophil phagocytosis was also examined. Results: HSR activation worsened lung endothelial (42%) and epithelial permeability (50%) to protein, decreased lung bacterial clearance (71%), and increased mortality (50%) associated with P. aeruginosa pneumonia, an effect that was not observed in heat-shock protein–72-null mice. HSR-mediated decrease in neutrophil phagocytosis (69%) and bacterial killing (38%) by macrophages was interleukin-10 dependent, a mechanism confirmed by increased lung bacterial clearance and decreased mortality (70%) caused by P. aeruginosa pneumonia in heat-shocked interleukin-10-null mice. Conclusions: Prior HSR activation worsens lung injury associated with P. aeruginosa pneumonia in mice via heat-shock protein–72- and interleukin-10-dependent mechanisms. These results provide a novel mechanism for the immunosuppression observed after severe trauma that is known to activate HSR in humans.

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