TLR4 Is Lower in Resistance-Trained Older Women and Related to Inflammatory Cytokines

McFarlin, Brian K.; Flynn, Michael G.; Campbell, Wayne W.; Stewart, Laura K.; Timmerman, Kyle L.

doi:10.1249/01.mss.0000145465.71269.10

Cited by 124 publications

(124 citation statements)

References 28 publications

(69 reference statements)

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“…Our results are supported by previous studies suggesting that physically active subjects present significantly lower cell surface TLR4 expression and inflammatory cytokine production than physically inactive subjects (Flynn et al 2003;Stewart et al 2005;McFarlin et al 2006). Therefore, it is plausible that low TLR2 and TLR4 expression inhibits proinflammatory cytokine production, which may explain, at least partially, the anti-inflammatory effect attributed to regular exercise (McFarlin et al 2004). …”

Section: Discussionsupporting

confidence: 90%

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

Rodriguez‐Miguelez

Fernandez‐Gonzalo

Almar

et al. 2014

AGE

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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.

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Section: Discussionsupporting

confidence: 90%

“…Toll-like receptors (TLR), in particular TLR2 and TLR4, may play an important role in the antiinflammatory effects of a physically active lifestyle (McFarlin et al 2004). TLRs bind to specific ligands, and the best described for TLR2 and TLR4 are peptidoglycan and lipopolysaccharide (LPS), respectively (Zbinden-Foncea et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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

Rodriguez‐Miguelez

Fernandez‐Gonzalo

Almar

et al. 2014

AGE

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“…ET is known to selectively deplete circulating CD16 + monocytes, inclusive of the (CD14 ++ CD16 + ) intermediate monocytes, possibly through exercise-induced transient spikes in endogenous glucocorticoids (67). Moreover, physical activity seems to be associated with reduced cell surface expression of Toll-like receptor 4 and a subsequent blunted inflammatory response to LPS (68). In conclusion, ET results in a favorable shift of monocytes in terms of both numbers and expression profile.…”

Section: Systemic Inflammationmentioning

confidence: 90%

Vascular Effects of Exercise Training in CKD

Craenenbroeck

Kouidi

et al. 2014

Clinical Journal of the American Society of Nephrology

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Cardiovascular disease remains the main cause of morbidity and mortality in patients with CKD, an observation that cannot be explained by the coexistence of traditional risk factors alone. Recently, other mechanisms, such as alterations in nitric oxide bioavailability, impaired endothelial repair mechanisms, inflammation, and oxidative stress (all characteristic in CKD), have gained much attention as mediators for the increased cardiovascular risk. Regular physical training is a valuable nonpharmacological intervention for primary and secondary prevention of cardiovascular disease. Likewise, the benefits of exercise training on exercise capacity and quality of life are increasingly recognized in patients with CKD. Furthermore, exercise training could also influence potential reversible mechanisms involved in atherosclerosis and arteriosclerosis. After discussing briefly the general concepts of vascular disease in CKD, this review provides an overview of the current evidence for the effects of exercise training at both clinical and preclinical levels. It concludes with some practical considerations on exercise training in this specific patient group.

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“…DS: diet-induced weight gain, sedentary; DE: diet-induced weight gain, forced treadmill running; NS: normal weight gain, sedentary previously reported in exercising humans. 6,7,22 To date the effect of exercise on mouse monocytes has not been extensively studied. Interestingly, the exercise effect was observed early in the training programme (at week 1), which leads us to speculate that forced treadmill running had a strong immune boosting effect demonstrated by altered monocyte TLR4 cell-surface expression.…”

Section: Discussionmentioning

confidence: 99%

“…Samples were prepared according to the standard technique. 6,7 Briefly, whole blood aliquots (10 mL) were incubated with an Fc receptor blocking cocktail (anti CD16/32) to reduce non-specific binding. Blocked cell pellets were labelled with either a three-colour positive (CD11b-PECy5, CD14-FITC and TLR4-PE) or a three-colour isotype control cocktail.…”

Section: Monocyte Cell-surface Tlr4 Measurementsmentioning

confidence: 99%

Defining a longitudinal survival model to examine forced treadmill running as a countermeasure for diet-induced weight gain

et al. 2010

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Diet-induced weight gain increases disease risk via disruption of the innate immune system. Flow cytometry is commonly used to assess the immune system; however, in mice such measurements traditionally require terminal procedures and tissue collection to generate sufficient sample. The present study refined an existing flow cytometry method to reduce the number of mice needed to longitudinally measure monocytes. CD-1 male mice were randomly assigned to one of the three groups: DS (diet-induced weight gain þ sedentary), DE (diet-induced weight gain þ forced treadmill running [total distance 35,755 + 1832 m]) or NS (normal weight gain þ sedentary). DS and DE consumed a 60% fat diet and NS consumed a 10% fat diet ad libitum. Saphenous vein blood samples were collected weekly for a period of six weeks and three-colour flow cytometry was used to measure changes in monocyte (CD11b þ /14 þ ) concentration and cell-surface toll-like receptor 4 (TLR4) expression. DS (18%) and DE (17%) gained more weight than NS (P , 0.001). On a group basis, DS expressed 17% more TLR4 than DE and NS (P ¼ 0.005). The present study demonstrates that a longitudinal survival model can be used to reduce the number of animals needed to complete flow cytometry experiments. Exercise during diet-induced weight prevented some (decreased monocyte TLR4 expression) but not all aspects of innate immune system function.

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TLR4 Is Lower in Resistance-Trained Older Women and Related to Inflammatory Cytokines

Cited by 124 publications

References 28 publications

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

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

Vascular Effects of Exercise Training in CKD

Defining a longitudinal survival model to examine forced treadmill running as a countermeasure for diet-induced weight gain

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