Heat shock protein suppresses the senescent lung cytokine response to acute endotoxemia.
BACKGROUND
Previous reports demonstrate that heat shock protein (HSP) can alter the pulmonary inflammatory cascade. We wished to determine if this mechanism is active in the senescent mouse.


METHODS
A dose-response and time-response curve for sodium arsenite (SA) induction of HSP was constructed. Eight 25-month-old B6C3F1 mice were given either 1, 2, 4, or 6 mg/kg SA. At 4 hours, the lungs were harvested and assayed for HSP by Western blot. Next, 8 mice were given 4 mg/kg SA and the lungs harvested at either 1, 2, 4, or 6 hours after injection and assayed for HSP. Next, 12 mice were prepared: Half received 4 mg/kg SA and 4 hours later, all received 0.5 mg/kg lipopolysaccharide (LPS). After 4 hours, lungs were harvested and Interleukin-1beta mRNA was assayed by Northern blot and semi-quantified by densitometry.


RESULTS
The optimum SA dose was determined to be 4 mg/kg. The maximum HSP production was at 4 hours. Mice receiving LPS only showed a marked increase (3-fold) in IL-1 message compared with the mice pretreated with SA.


CONCLUSIONS
These data suggest that in the senescent as in the mature mouse lung, HSP downregulates the inflammatory cascade in response to LPS.
LoCicero
J
J
Section of General Thoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. locicero@harvarda.harvard.edu
Xu
X
X
Zhang
L
L
D000208:Acute Disease; D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D016922:Cellular Senescence / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000502:physiology*; D007375:Interleukin-1 / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D017670:Sodium Compounds / Q000494:pharmacology; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology
D018053:Arsenites; D004791:Enzyme Inhibitors; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017670:Sodium Compounds; C017947:sodium arsenite