Age-associated Differences in Cardiovascular Inflammatory Gene Induction during Endotoxic Stress

Hiroshi Saito, John Papaconstantinou

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Upon physiological stress, families of stress response genes are activated as natural defense mechanisms. Here, we show that induction of specific inflammatory genes is significantly dysregulated and altered in the heart of aged (24-26-month-old) versus young (4-month-old) mice experimentally challenged with a bacterial endotoxin, lipopolysaccharide (LPS, 1.5 mg/kg of body mass). Whereas the LPS-mediated induction of cardiac mRNA for tumor necrosis factor α or inducible nitric-oxide synthase showed no age-associated differences, the induction of interleukin-1β (IL-1β) and intracellular adhesion molecule-1 was modestly extended with aging, and the induction of IL-6 was significantly prolonged with aging. This age-associated phenomenon occurred gradually from 4 to 17 months of age and became more evident after 23 months of age. The age-associated augmentation of the cardiac IL-6 induction was also dramatic at the protein level. Immunohistochemically, the LPS-induced cardiac IL-6 was localized mainly in the microvascular walls. Aged but not young mice showed a high mortality rate during these experiments. These results demonstrate that endotoxin-mediated induction of specific inflammatory genes in cardiovascular tissues is altered with aging, which may be causally related to the increased susceptibility of aged animals to endotoxic stress.

Original languageEnglish (US)
Pages (from-to)29307-29312
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number31
DOIs
StatePublished - Aug 3 2001

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Interleukin-6
Genes
Aging of materials
Endotoxins
Physiological Stress
Nitric Oxide Synthase Type II
Interleukin-1
Lipopolysaccharides
Animals
Adhesion
Tumor Necrosis Factor-alpha
Tissue
Messenger RNA
Molecules
Mortality
Proteins
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Age-associated Differences in Cardiovascular Inflammatory Gene Induction during Endotoxic Stress. / Saito, Hiroshi; Papaconstantinou, John.

In: Journal of Biological Chemistry, Vol. 276, No. 31, 03.08.2001, p. 29307-29312.

Research output: Contribution to journalArticle

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