ABSTRACT
Title
Hsp72 response and lung inflammation after chronic stress
Authors
M. Pannacci, V. Lucini, S. Dugnani and F. Scaglione
Department of Pharmacology, Chemotherapy and Toxicology, Faculty of Medicine, University of Milan, via Vanvitelli 32, 20129 Milan, Italy.
Department of Pharmacology, Chemotherapy and Toxicology, Faculty of Medicine, University of Milan, via Vanvitelli 32, 20129 Milan, Italy.
Abstract
Physical exercise can induce a stress response with a range of stressors that ultimately challenge cellular homeostasis. All cell respond to stress through the stimulation of the synthesis of heat shock protein (HSPs) which acts as molecular chaperones to maintain cellular homeostasis. In particular, exercise induces the expression of Hsp 72 in a number of central and peripheral tissues and this response is both intensity and duration dependent.
Hsp 70 is associated with improved cellular survivability, tolerance to stressors and cytoprotective effects. The induction of Hsp 72 gene transcription represses proinflammatory cytokines genes transcription by inhibiting NF-kB.
Moreover the expression of Hsp72 is well described in both whole lungs and in specific lung cells in response to stressors and has an important cytoprotective role during lung inflammation and injury. Some studies showed that Hsp 72 is detectable in pulmonary edema fluid in patients with acute lung injury.
The aim of our work was to evaluate a correlation between expression of proinflammatory cytokines (TNFα ; IL1β ; ICAM1; MCP1) and expression of Hsp72 in lung tissues, in a murine model of physical stress also considering the susceptibility to respiratory tract infection (RTI).
Mice Balb/C were subjected to swimming for 1 h/day for 4 weeks; after chronic exercise, animals were infected with 1x10^8CFU of S. Pneumoniae. Changes in expression of proinflammatory cytokines and Hsp72 were evaluated by Real Time PCR on RNA extracted from whole lungs. Infection was evaluated by bacterial count.
Hsp72 expression increased significantly during 4 week of exercise (p<0.05), additionally this expression showed to attenuate proinflammatory cytokines release (p<0.05) in stressed animals.
In chronic stressed group, this decrease is maintained even 24h or 48h after infection with S. Pneumoniae. Bacterial size was significantly higher (p< 0.001) in chronic stressed animals vs controls (7x10^6 ± 3,5 CFU/lung vs 3.5x10^4 ± 1.5 CFU/lung).
Data obtained confirmed that in chronic exercise increased levels of Hsp72 , but we showed for the first time that the contemporary decrease of proinflammatory cytokines is associated to an increased risk of RTI.
Hsp 70 is associated with improved cellular survivability, tolerance to stressors and cytoprotective effects. The induction of Hsp 72 gene transcription represses proinflammatory cytokines genes transcription by inhibiting NF-kB.
Moreover the expression of Hsp72 is well described in both whole lungs and in specific lung cells in response to stressors and has an important cytoprotective role during lung inflammation and injury. Some studies showed that Hsp 72 is detectable in pulmonary edema fluid in patients with acute lung injury.
The aim of our work was to evaluate a correlation between expression of proinflammatory cytokines (TNFα ; IL1β ; ICAM1; MCP1) and expression of Hsp72 in lung tissues, in a murine model of physical stress also considering the susceptibility to respiratory tract infection (RTI).
Mice Balb/C were subjected to swimming for 1 h/day for 4 weeks; after chronic exercise, animals were infected with 1x10^8CFU of S. Pneumoniae. Changes in expression of proinflammatory cytokines and Hsp72 were evaluated by Real Time PCR on RNA extracted from whole lungs. Infection was evaluated by bacterial count.
Hsp72 expression increased significantly during 4 week of exercise (p<0.05), additionally this expression showed to attenuate proinflammatory cytokines release (p<0.05) in stressed animals.
In chronic stressed group, this decrease is maintained even 24h or 48h after infection with S. Pneumoniae. Bacterial size was significantly higher (p< 0.001) in chronic stressed animals vs controls (7x10^6 ± 3,5 CFU/lung vs 3.5x10^4 ± 1.5 CFU/lung).
Data obtained confirmed that in chronic exercise increased levels of Hsp72 , but we showed for the first time that the contemporary decrease of proinflammatory cytokines is associated to an increased risk of RTI.