| 10543471 |
LoCicero J 3rd, Xu X, Zhang L: Heat shock protein suppresses the senescent lung cytokine response to acute endotoxemia. Ann Thorac Surg. 1999 Oct;68(4):1150-3.
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. |
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