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

Abstract

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, phosphop38, 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.

Effects of aerobic training on markers of autophagy in the elderly

“…Other investigations have previously failed to show aerobic exercise-induced changes in TLR2 and TLR4 signaling pathways after a 15-day endurance program in diabetic patients (Reyna et al 2013) or after 10 weeks of endurance training in obese athletes (Nickel et al 2011). Yet, the current data contrast with previous results from our group indicating that other exercise modalities (resistance exercise or whole-body vibration training) downregulate TLR expression in old subjects, resulting in a less proinflammatory state (Rodriguez-Miguélez et al 2014. Thus, despite the improved exercise capacity induced by the training protocol employed in the present study, results indicate that the current training failed to induce significant alterations in TLR2 and TLR4 pathways.…”

“…*p < 0.05 vs CG; #p < 0.05 vs Pre within a group not seem to be related to a parallel downregulation of TLR2 and TLR4 MyD88 or TRIF-dependent pathways, since we could not identify any significant change in these markers after the training period. Since other training modalities (i.e., resistance exercise) induced TLR2 and TLR4 adaptations (Fernandez-Gonzalo et al 2012Rodriguez-Miguélez et al 2014, the lack of an apparent relationship between autophagy and TLRs may be due to the exercise training mode currently employed, at least to some extent.…”

Strength Training Decreases Inflammation and Increases Cognition and Physical Fitness in Older Women with Cognitive Impairment

“…The increased concentrations of IL-10 found in our exercise group corroborate other findings involving cytokines and its response to exercise programs in older persons (Rodriguez-Miguelez et al, 2014). This mechanism is supported by the immunoregulatory effect of exercise practice that increases IL-10 and attenuates TNF-α levels (Moldoveanu et al, 2001).…”

Exercise has the guts: How physical activity may positively modulate gut microbiota in chronic and immune-based diseases

“…In young women, eccentric exercise was accompanied by blunted, TLR4-mediated, inflammatory responses [59]. Resistance exercise ameliorated the pro-inflammatory status of elderly subjects through an attenuation of TLR2 and TLR4 signaling pathways [60]. By contrast, strenuous, prolonged endurance exercise may reduce gastrointestinal blood flow [61], leading to hypo-perfusion [62,63], susceptibility to endotoxins ("leaky gut", endotoxemia) [64], and an overall increased expression of pro-inflammatory modulators (TNF-, IL-1, IL-6, IL-1ra) [56,65,66].…”