Effects of eccentric exercise on toll-like receptor 4 signaling pathway in peripheral blood mononuclear cells

Abstract

Cuevas MJ, González-Gallego J. Effects of eccentric exercise on tolllike receptor 4 signaling pathway in peripheral blood mononuclear cells. J Appl Physiol 112: 2011-2018, 2012. First published March 29, 2012 doi:10.1152/japplphysiol.01499.2011This study aimed to investigate the response of the toll-like receptor 4 (TLR4) signaling pathway to an acute bout of eccentric exercise, and to assess whether eccentric training attenuated the effects induced by acute eccentric exercise. Twenty men (22.4 Ϯ 0.5 yr) were divided into a control group (CG, n ϭ 8) and a training group (TG, n ϭ 12). Both groups performed two acute eccentric bouts on a squat machine in a 9-wk interval. During this time, TG followed a 6-wk eccentric training program (3 session/wk; 3-5 sets of 10 repetitions with loads ranging between the 40 and 50% of maximal isometric voluntary contraction). CD14, TLR4, and TNF-␣ mRNA levels, and CD14, TLR4, myeloid differentiation factor 88, tumor necrosis factor receptor-associated factor 6, TIR-domain-containing adapterinducing interferon-␤, phospho-IB kinases, phospho-IB, phospho-ERK-1/2, and TNF-␣ protein concentration were measured in peripheral blood mononuclear cells, before, immediately, and 2 h after each eccentric bout. The first acute eccentric bout triggered a proinflammatory response mediated by an upregulation of all of the factors measured within the TLR4 signaling pathway. Following the training period and after the second acute bout, CG showed a similar proinflammatory response than that seen after the first bout. However, the eccentric training intervention decreased significantly the protein concentration of all factors analyzed in TG compared with results obtained after the first bout. These results suggest that the TLR4-signaling pathway plays a critical role in the proinflammatory response seen after acute eccentric exercise. This response was attenuated after an eccentric training program through myeloid differentiation factor 88-dependent and -independent pathways.

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

“…This protein is essential to stimulate pro-inflammatory cytokine production (Kawai and Akira 2006). Previous results from our group indicate that the MyD88-dependent pathway plays an important role in the inflammatory response induced by eccentricbased resistance exercise (Fernandez-Gonzalo et al 2012. In support, data from the current investigation suggest that the lower TLR2 and TLR4 expression induced by resistance training was accompanied by a decrease in MyD88 protein concentration in PBMC of old subjects.…”

“…Therefore, physical activity, but not age, is more important for TLR4 signaling and inflammatory cytokine production . Supporting these data, eccentric-based resistance training prevented exerciseinduced pro-inflammatory responses in the elderly (Jimenez-Jimenez et al 2008), and 6 weeks of eccentric resistance exercise reduced TLR4-mediated activation of the pro-inflammatory response through MyD88-dependent and MyD88-independent pathways in young men (Fernandez-Gonzalo et al 2012). To this background, it is hypothesized that an 8-week resistance exercise training program would reduce the inflammation in elderly subjects through the TLR2 and TLR4 signaling pathway.…”

Effects of aerobic training on markers of autophagy in the elderly

“…*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.…”

“…Thus, the welldocumented anti-inflammatory effects of exercise in the elderly could be potentially related to changes in the autophagic capacity. In fact, several investigations have reported the effect of aerobic and resistance exercise training modalities on TLR2 and TLR4 signaling pathways (Gleeson et al 2006;Fernandez-Gonzalo et al 2012, and we have recently shown that resistance or whole-body vibration training may improve the anti-inflammatory status in peripheral blood mononuclear cells (PBMCs) from elderly subjects through an attenuation of MyD88-and TRIFdependent TLR signaling pathways (RodriguezMiguélez et al 2014(RodriguezMiguélez et al , 2015.…”

Exercise, fitness, and the gut

“…Frequent physical activity is also associated with reduction of toll-like receptors on monocytes and macrophages and attendant antiinflammatory effects. This is particularly true of eccentric exercise and resistance training [49][50][51].…”