Endotoxin inhibitor blocks heat exposure-induced expression of brain cytokine mRNA in aged rats

Toshihiko Katafuchi, Atsushi Takaki, Sachiko Take, Tetsuya Kondo, Megumu Yoshimura

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

To investigate the age-related changes in the expression of interleukin-1β (IL-1β) and its related substances in the brain during heat stress, we measured amounts of mRNAs for IL-1β, cyclooxygenase-2 (COX-2), and an inhibitor of nuclear factor (NF)-κB-β (IκB-β) that is known to reflect an activation of NF-κB, in the cortex, cerebellum, and hippocampus using a quantitative real-time capillary PCR method. The basal levels of IL-1β mRNA in aged rats (108-110 weeks old) was significantly higher than those in young animals (10-11 weeks old) in these brain regions. Heat exposure (33°C) for 1 h enhanced the expression of IL-1β and COX-2 mRNAs in aged rats but not in young ones. The amount of lipopolysaccharide (LPS) assessed by its bioactivity in the cortex increased by heat exposure only in aged rats. To further examine an involvement of LPS in the increase in mRNAs, an endotoxin inhibitor (EI), a synthetic peptide that detoxifies LPS by binding to the toxic component of LPS, lipid A, was intraperitoneally injected before heat exposure in aged rats. An intraperitoneal injection of EI significantly attenuated the heat exposure-induced increases in mRNAs for IL-1β, COX-2, IκB-β, and the LPS activity. Administration of EI also debilitated the heat exposure-induced hyperthermia and responses of plasma ACTH and catecholamines. These findings, taken together, suggest that the bacterial translocation is involved in the mechanisms of the responses to heat exposure in aged rats including the increased expression of mRNAs for IL-1β and its related substances in the brain.

Original languageEnglish
Pages (from-to)24-32
Number of pages9
JournalMolecular Brain Research
Volume118
Issue number1-2
DOIs
Publication statusPublished - Oct 21 2003

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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