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.
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.
authors.affiliation: Department of Health and Sports Science, Kawasaki University of Medical Welfare, Kurashiki, Okayama, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Uchida
authors.affiliation: Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Shinjuku, Tokyo, Japan; Research Institute of Health and Welfare, Kibi International University, Takahashi, Okayama, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Oyanagi
authors.affiliation: Graduate School of Sport Sciences, Waseda University, Tokorozawa, Saitama, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kawanishi
authors.affiliation: Faculty of Sport and Health Science, Ritsumeikan University, Kusatsu, Shiga, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Iemitsu
authors.affiliation: Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Shinjuku, Tokyo, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Miyachi
authors.affiliation: Department of Health and Sports Science, Kawasaki University of Medical Welfare, Kurashiki, Okayama, Japan.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kremenik
authors.affiliation: Department of Health and Sports Science, Kawasaki University of Medical Welfare, Kurashiki, Okayama, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Onodera
authors.affiliation: Department of Health and Sports Science, Kawasaki University of Medical Welfare, Kurashiki, Okayama, Japan. Electronic address: yanohiro@mw.kawasaki-m.ac.jp.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yano
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D018938:Caco-2 Cells; D002867:Chromones / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005408:Flagellin / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007420:Intestine, Large / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010805:Physical Conditioning, Animal; D005082:Physical Exertion / Q000276:immunology*; D011433:Propranolol / Q000494:pharmacology; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002867:Chromones; D018836:Inflammation Mediators; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051198:Toll-Like Receptor 5; D014409:Tumor Necrosis Factor-alpha; D005408:Flagellin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011433:Propranolol; D004837:Epinephrine
keywords: Caco2; Epinephrine; PI3K; RAW264; TLR5