title: Attenuation of exercise effect on inflammatory responses via novel role of TLR4/PI3K/Akt signaling in rat splenocytes.
abstract: Moderate exercise diminishes proinflammation cytokine production in various types of immune cells, but the intracellular signaling pathways involved are not completely understood. Phosphoinositide 3-kinase (PI3K)/Akt, a crucial downstream protein of toll-like receptor 4 (TLR4), may modulate inflammation. The present study aimed to investigate the effects of exercises on lipopolysaccharide (LPS)-stimulated inflammatory response in splenocytes and to explore potential mechanisms of the PI3K/Akt pathway. Male rats were divided into sedentary and exercise groups. Animals in the exercise group underwent endurance training 30 min/day, 7 days/wk, at the speed of 20 m/min on a treadmill for 1 wk. Here, we showed that exercise 1) attenuated TLR4, 2) increased PI3K/phospho-Akt (p-Akt), and 3) diminished phospho-nuclear factor-κB (p-NF-κB) expression. In addition, administration of splenocytes isolated from trained rats with LPS in vitro showed 1) reduced tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and nitric oxide secretion and 2) decreased splenocyte proliferation. The plasma corticosterone (CCS) level in the exercise group was higher than that in the sedentary group. We confirmed that CCS down-regulated TNF-α and IL-6 secretion in response to LPS in rat splenocytes. Dexamethasone also significantly attenuated LPS-evoked release of TNF-α and IL-6 in a dose-dependent manner. These findings suggested that exercise dampened the secretion of inflammation mediators probably through partial inhibition of TLR4 and p-NF-κB and activation of PI3K/p-Akt expression in the spleen.
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Jian
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Po-Han
authors.initials: PH
authors.lastname: Lin
authors.affiliation: Medical Center of Aging Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Jou-Chun
authors.initials: JC
authors.lastname: Chou
authors.affiliation: Department of Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Hsueh-Su
authors.initials: HS
authors.lastname: Teng
authors.affiliation: Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Sindy
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Fu-Kong
authors.initials: FK
authors.lastname: Lieu
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Medical Center of Aging Research, China Medical University Hospital, Taichung, Taiwan; Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; and pswang@ym.edu.tw.
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
authors.affiliation: Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shyi-Wu
authors.initials: SW
authors.lastname: Wang
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D002478:Cells, Cultured; D007249:Inflammation / Q000276:immunology* / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000276:immunology; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D018836:Inflammation Mediators; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: TNF-α; corticosterone; exercise training; phosphoinositide 3-kinase (PI3K)/Akt; splenocytes; toll-like receptor 4