Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects

• Published in: AGE Vol. 36; no. 6; p. 9734
• Main Authors: Rodriguez-Miguelez, Paula, Fernandez-Gonzalo, Rodrigo, Almar, Mar, Mejías, Yubisay, Rivas, Ana, de Paz, José A., Cuevas, María J., González-Gallego, Javier
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 2014; Springer Nature B.V
• Subjects: Adaptor proteins; Age; Aged; Aging; Aging - metabolism; Aging - physiology; Analysis of Variance; Anthropometry; Biomedical and Life Sciences; Blotting, Western; C-reactive protein; C-Reactive Protein - metabolism; Cell Biology; Chronic illnesses; Cytokines; Down-Regulation; Exercise; Extracellular signal-regulated kinase; Female; Fitness training programs; Geriatric Assessment - methods; Geriatrics/Gerontology; Heat shock proteins; Hsp60 protein; Hsp70 protein; Humans; Immune system; Inflammation; Inflammation - metabolism; Inflammation - physiopathology; Inflammation Mediators - blood; Interferon; Interferon regulatory factor; Interferon regulatory factor 7; Interleukin-6 - metabolism; Kinases; Leukocytes (mononuclear); Life Sciences; Ligands; Male; Medical screening; Medicin och hälsovetenskap; Molecular Medicine; mRNA; Muscle Contraction - physiology; Muscle, Skeletal - physiology; MyD88 protein; Peripheral blood mononuclear cells; Physical fitness; Physical training; Physiology; Plasma levels; Proteins; Resistance Training - methods; Reverse Transcriptase Polymerase Chain Reaction - methods; Signal transduction; Signal Transduction - physiology; Strength training; TLR2 protein; TLR4 protein; Toll-Like Receptor 2 - blood; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - blood; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Inflammation; TLR; Elderly; MyD88; Resistance exercise
• ISSN: 0161-9152; 2509-2715; 1574-4647; 1574-4647; 2509-2723
• DOI: 10.1007/s11357-014-9734-0

This study assessed the effects of a resistance exercise training program on the inflammatory response associated with Toll-like receptor (TLR) 2 and TLR4 signaling pathways in senior participants. Twenty-six healthy subjects (age, 69.5 ± 1.3) were randomized to a training (TG; n  = 16) or a control (CG; n  = 10) group. TG performed an 8-week resistance training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and levels of proteins involved in the TLR2, TLR4, and myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways were analyzed. The inflammatory status was evaluated through messenger RNA (mRNA) and protein content of interleukin (IL)-10 and tumor necrosis factor alpha (TNF-α) and plasma levels of C-reactive protein (CRP). After the 8-week resistance training, TLR2 and TLR4 protein expression was reduced in TG. MyD88, p65, phospho-p38, TIR domain-containing adaptor inducing interferon (TRIF), IKKi/IKKε, phospho-interferon regulatory factor (IRF) 3, and phosho-IRF7 were also downregulated in TG after the intervention. The training program induced an increase of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Hsp70 and a reduction of Hsp60. While TNF-α mRNA and protein values remained unchanged in both TG and CG, IL-10 mRNA and protein content were upregulated in TG after the intervention. CRP values decreased in TG only. The increase in Hsp70 negatively correlated with TLR2 and TLR4 downregulation. These data suggest that resistance exercise may represent an effective tool to ameliorate the pro-inflammatory status of old participants through an attenuation of MyD88-dependent and MyD88-independent TLR2 and TLR4 signaling pathways.