Exhaustive exercise increases the TNF-α production in response to flagellin via the upregulation of toll-like receptor 5 in the large intestine in mice

Masataka Uchida, Eri Oyanagi, Noriaki Kawanishi, Motoyuki Iemitsu, Motohiko Miyachi, Michael J. Kremenik, Sho Onodera, Hiromi Yano*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Although intense exercise may induce temporary immune depression, it is unclear whether exercise stimulates tumor necrosis factor-alpha (TNF-α) production in response to flagella protein flagellin (FG), which binds to toll-like receptor 5 (TLR5) and induces the production of pro-inflammatory cytokines. Male C3H/HeN mice were administered FG (1. mg/kg, i.v.) after exhaustive exercise (EX), and the plasma TNF-α concentrations were examined. The production of TNF-α and the TLR5 expression in both RAW264 and Caco2 cells were measured under FG conditions in vitro. Although the plasma TNF-α concentrations were observed to significantly increase in both the EX and non-EX (N-EX) mice (p< 0.01, respectively) following FG injection, the TNF-α levels in the EX mice were significantly higher than those observed in the N-EX mice (p< 0.01). Epinephrine (Ep) treatment accelerated the FG-induced TNF-α production and TLR5 expression on the Caco2, but not RAW264 cells. Interestingly, a high Ep-induced TLR5 expression was observed on the Caco2 cell surface, which was inhibited by an inhibitor of phosphoinositide3-kinase (PI3K), Ly294002, as well as a β-adrenergic blocker, propranolol. In addition, the EX-induced TNF-α production observed in response to FG was also attenuated by pretreatment with propranolol. Our findings suggest that exhaustive exercise upregulates the production of TNF-α in response to FG via a high expression of TLR5 on the intestinal cell surface following the stimulation of β-adrenergic receptors with exercise.

Original languageEnglish
Pages (from-to)151-158
Number of pages8
JournalImmunology Letters
Volume158
Issue number1-2
DOIs
Publication statusPublished - 2014 Mar
Externally publishedYes

Keywords

  • Caco2
  • Epinephrine
  • PI3K
  • RAW264
  • TLR5

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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