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TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women.

ABSTRACT: This study assessed the inflammatory response mediated by the toll-like receptor 4 (TLR4) signaling pathway after acute eccentric exercise before and after an eccentric training program in women. Twenty women performed two acute eccentric bouts using a squat machine over a ~9 week interval. The training group (TG) carried out an eccentric training program during 6 weeks, while the control group (CG) did not follow any training. Protein content of markers involved in the TLR4-mediated activation of several nuclear transcription factors, such as nuclear factor ?B (NF-?B), and interferon regulatory transcription factor 3 (IRF3), was analyzed. The inflammatory response after the first acute bout was similar between TG and CG, showing an upregulation of all the markers analyzed, with the exception of IRF3. After the second bout, the upregulation of TLR4 signaling pathway was blunted in TG, but not in CG, through both the myeloid differentiation factor 88- and toll/interleukin-1 receptor domain containing adapter inducing interferon-?-dependent pathways. These results highlight the role of the TLR4 in controlling the exercise-induced inflammatory response in young women. More importantly, these data suggest eccentric training may help to prevent TLR4 activation principally through NF-?B, and perhaps IRF3, downstream signaling in this population.

SUBMITTER: Fernandez-Gonzalo R

PROVIDER: S-EPMC4175753 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women.

Fernandez-Gonzalo Rodrigo R De Paz José A JA Rodriguez-Miguelez Paula P Cuevas María J MJ González-Gallego Javier J

Mediators of inflammation 20140909

This study assessed the inflammatory response mediated by the toll-like receptor 4 (TLR4) signaling pathway after acute eccentric exercise before and after an eccentric training program in women. Twenty women performed two acute eccentric bouts using a squat machine over a ~9 week interval. The training group (TG) carried out an eccentric training program during 6 weeks, while the control group (CG) did not follow any training. Protein content of markers involved in the TLR4-mediated activation ...[more]

PMID: 25294957

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Project description:BackgroundAvenanthramides (AVA) are a group of di-phenolic acids found only in oats and have shown antioxidant and anti-inflammatory effects in vitro and in vivo. Eccentric muscle contraction is intimately involved in rigorous exercise that activates systemic and local inflammatory responses. The objective of the study is to evaluate whether chronic AVA supplementation could attenuate peripheral inflammatory and immunological markers in human subjects in response to an acute bout of downhill running (DR).MethodsEleven male and thirteen female subjects voluntarily participated in this double-blinded, randomized controlled study and were randomly divided into AVA-supplemented (AVA) or control (C) groups. All subjects conducted a DR protocol at - 10% grade with an intensity equivalent to 75% of their maximal heart rate. Blood samples were collected at rest and various time points (0-72 h) after DR (PRE). After an 8-week washout period, participants received two cookies daily containing either 206 mg/kg (AVA) or 0 mg/kg (C) AVA for 8 weeks. Following the oat supplementation regimen, the DR and blood sampling protocols were repeated (POST). Plasma inflammatory and immunological markers were measured using Multiplex immunoassay and muscle soreness was evaluated with pain rating scale.ResultsDR increased plasma creatine kinase (CK) activity (P < 0.01) during PRE, but the response was reduced at 24 and 48 h during POST vs. PRE regardless of AVA status (P < 0.05). Neutrophil respiratory burst (NRB) levels were elevated at 4 and 24 h (P < 0.05) during PRE but were significantly decreased at 0-48 h during POST vs. PRE (P < 0.05 or 0.01). Granulocyte-colony stimulating factor (G-CSF), the neutrophil stimulating cytokine, was also increased in response to DR but showed lower levels in AVA compared to C during POST vs. PRE (P < 0.05). Plasma interleukin-6 (IL-6) content showed an increase at 0 and 4 h during PRE and 0 h during POST (P < 0.01), whereas during POST there was a trend toward a lower IL-6 level in AVA vs. C (P = 0.082). Plasma levels of anti-inflammatory agent interleukin-1 receptor antagonist (IL-1Ra) showed an increase at 4 h during PRE, and was significantly elevated in AVA vs. C during POST. Both soluble vascular cell adhesion molecule-1 (sVCAM-1) and monocyte chemoattractant protein-1 (MCP-1) contents increased at 0 and 24 h post DR during PRE as well as POST sessions, however, sVCAM-1 content was lower in AVA vs. C during POST (P < 0.05) and MCP-1 levels were below resting level at 24, 48 and 72 h during POST (P < 0.05). DR increased muscle pain at all post-DR time points (P < 0.01), but the pain level was alleviated by oat supplementation at 48 and 72 h during POST regardless of AVA treatment (P < 0.05).ConclusionsOat AVA supplementation reduced circulatory inflammatory cytokines and inhibited expression of chemokines and cell adhesion molecules induced by DR.Trial registrationClinicalTrials.gov identifier: NCT02584946 . Registered 23 October 2015.

Project description:BackgroundThe in-vivo regulation of vascular conductance (VC) is a continuous balance between endothelial vasodilation and sympathetic vasoconstriction. Although women may report blunted sympathetic vasoconstriction along with higher endothelial vasodilation than men, it is currently unknown whether the interaction between vasoconstriction and vasodilation leads to different regulation of VC between sexes. This study assessed sex differences in sympathetic-mediated blunting of endothelial vasodilation after a brief period of ischemia and whether any restriction of vasodilation blunts tissue blood flow (BF) and re-oxygenation.Methods13 young women and 12 young men underwent two 5-min forearm circulatory occlusions followed by reperfusion, one in basal conditions and the other during cold pressor test-induced sympathetic activation (SYMP). Brachial artery diameter and BF, mean arterial pressure, total peripheral resistance (TPR), and thenar eminence oxygenation were collected. Percent changes normalized to baseline values of forearm VC, brachial artery BF and flow-mediated dilation (FMD), TPR, and hand oxygenation after circulatory reperfusion were calculated.ResultsTPR increased during SYMP in men (p = 0.019) but not in women (p = 0.967). Women showed a greater brachial artery FMD than men (p = 0.004) at rest, but sex differences disappeared after normalization to shear rate and baseline diameter (p > 0.11). The percent increases from baseline of peak and average forearm VC after circulatory reperfusion did not differ between sexes in basal conditions (p > 0.98) or during SYMP (p > 0.97), and were restrained by SYMP similarly in both sexes (p < 0.003) without impairing the hand re-oxygenation (p > 0.08) or average hyperemic response (p > 0.09).ConclusionsAlthough women may report blunted sympathetic vasoconstriction than men when assessed separately, the similar sympathetic-mediated restriction of vasodilation suggests a similar dynamic regulation of VC between sexes. SYMP-mediated restrictions of the normal forearm vasodilation do not impair the average hyperemic response and hand re-oxygenation in both sexes.

Dataset Information

TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women.

Publications

TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women.

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