CD14+ Cell-Surface Expression of Toll-like Receptor 4 is Lower in Exercise Trained Older Women

Abstract

1054 PURPOSE: Inflammatory cytokines are associated with an increased risk of cardiovascular disease, diabetes mellitus, cachexia, and osteoporosis and are often increased in age-advanced persons. Toll-like receptor 4 (TLR4) is the primary signaling receptor for lipopolysaccharide (LPS) and TLR4 signaling stimulates inflammatory cytokine production. Thus, TLR4 may explain lower LPS-stimulated cytokine expression we have observed in older, trained persons. The purpose of the present study was to compare the effect of both acute (3 sets of 8 reps for 9 exercises at 80% of the 1RM) and chronic resistance exercise on CD14+ cell-surface expression of TLR4. METHODS: Blood samples were collected from trained (TR, n = 10, > 6 months of resistance exercise) or untrained (UT, n = 10), older (65–80 yrs) post-menopausal women before, immediately after, 2-h, 6-h, and 24-h after exercise. Cell-surface expression of TLR4 was determined by two-color immunocytometry. LPS-stimulated (LPS, 25 μg.ml−1) whole-blood production of IL-6, IL-1β, and TNF-α were determined by ELISA. Plasma IL-6 and TNF-α were analyzed by ELISA. After cell-surface TLR4 analysis, subjects were placed into groups of high and low TLR4 “expressers” (HI and LO) and group comparisons for IL-6, TNF-α, and IL-1β were made. RESULTS: There was 124% lower TLR4 cell-surface expression in TR than UT, but no significant effects were found for plasma (IL-6 & TNF-α) or mRNA expression (IL-6, TNF-α, & IL-1β) of inflammatory cytokines. A significant time effect was found for LPSstimulated IL-6, IL-1β, and TNF-α, where 6-h was significantly greater than all other samples. HI produced more LPS-stimulated TNF-α (302%), IL-1β (209%), and IL-6(167%) than LO. CONCLUSION: Acute exercise did not alter TLR4 expression; but TR expressed 2.3-fold less TLR4 than UT, suggesting that chronic exercise alters TLR4. Despite a difference in cell-surface TLR4, plasma, mRNA, and LPS-stimulated inflammatory cytokine were not different between groups. High TLR4 expressers produced significantly more LPS-stimulated IL-6, TNF-α, and IL-1β than low TLR4 expressers.