RRC ID 44849
Author Uchida M, Oyanagi E, Kawanishi N, Iemitsu M, Miyachi M, Kremenik MJ, Onodera S, Yano H.
Title 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.
Journal Immunol Lett
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 (1mg/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.
Volume 158(1-2)
Pages 151-8
Published 2014-3
DOI 10.1016/j.imlet.2013.12.021
PII S0165-2478(14)00003-0
PMID 24412598
MeSH Adrenergic beta-Antagonists / pharmacology Animals Caco-2 Cells Chromones / pharmacology Epinephrine / pharmacology Flagellin / administration & dosage Flagellin / immunology* Humans Inflammation Mediators / blood Intestine, Large / immunology* Male Mice Mice, Inbred C3H Morpholines / pharmacology Phosphoinositide-3 Kinase Inhibitors Physical Conditioning, Animal* Physical Exertion / immunology* Propranolol / pharmacology Toll-Like Receptor 5 / genetics Toll-Like Receptor 5 / metabolism* Tumor Necrosis Factor-alpha / biosynthesis* Tumor Necrosis Factor-alpha / blood Tumor Necrosis Factor-alpha / genetics Up-Regulation / drug effects
IF 2.552
Times Cited 6
Human and Animal Cells