TLR4 is lower in resistance-trained older women and related to inflammatory cytokines.
OBJECTIVE
Regular exercise may offset age-associated increases in inflammatory cytokines and reduce the risk of developing diseases with an inflammatory etiology by exerting "anti-inflammatory" effects. Toll-like receptor 4 (TLR4) signaling stimulates inflammatory cytokine production, and may explain the "anti-inflammatory" effect attributed to regular exercise. Therefore, the purpose of the present study was to compare the effect of acute (3 sets, 9 exercises, 10 repetitions at 80% of the 1-repetition maximum) and chronic resistance exercise on TLR4 and inflammatory cytokines.


METHODS
Venous blood samples were collected from trained (TR, N = 10) and untrained (UT, N = 10) older (65-80 yr) postmenopausal women: before (PRE), immediately post (POST), and 2 h (2H), 6 h (6H), and 24 h (24H) after completion of exercise. Cell-surface expression of TLR4 (two-color immunofluorescent cytometry), LPS (25 microg x mL(-1))-stimulated cytokine production (ELISA), plasma cytokines (ELISA), and mRNA expression of TLR4 and cytokines (RT-PCR) were determined for each sample.


RESULTS
TR had 124% less cell-surface TLR4 expression than UT (P < 0.05). A significant time effect was found for LPS-stimulated IL-6, IL-1beta, and TNF-alpha, where 6H was significantly greater than all other samples. No significant effects were found for plasma (IL-6 and TNF-alpha) or mRNA expression (IL-6, TNF-alpha, and IL-1beta) of inflammatory cytokines. When subjects were grouped according to cell-surface TLR4 expression (HI and LO), LPS-stimulated TNF-alpha (302%), IL-1beta (209%), and IL-6 (167%) production was greater for HI than LO (P < 0.05).


CONCLUSIONS
Regularly exercising older women expressed less cell-surface TLR4 but did not have lower plasma levels or produce less LPS-stimulated inflammatory cytokines at rest or in response to a single bout of resistance exercise. TLR4 changes may explain the "anti-inflammatory" effect that has recently been attributed to chronic (2x wk for previous 24 months) resistance exercise training.
McFarlin
Brian K
BK
Laboratory of Integrated Physiology, Department of Health and Human Performance [corrected] University of Houston, Houston, TX, USA. bkmcfarlin@att.net
Flynn
Michael G
MG
Campbell
Wayne W
WW
Stewart
Laura K
LK
Timmerman
Kyle L
KL
D000222:Adaptation, Physiological / Q000502:physiology; D000368:Aged / Q000502:physiology*; D001772:Blood Cell Count; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism*; D004032:Diet; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology*; D017698:Postmenopause; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014891:Weight Lifting / Q000502:physiology*
D016207:Cytokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors