Inflammation, exercise and aging: Are toll -like receptors the common link?

Laura Kathleen Stewart, Purdue University

Abstract

The purpose of this research was to examine whether age, physical activity level, or exercise training influence cell-surface expression of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) and to determine to what extent these changes are related to differences in stimulated and plasma inflammatory cytokine levels (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β)), and serum levels of high sensitivity C-reactive protein (hsCRP). Subjects (n = 60) were assigned to: young physically active (YPA, n = 15; 25.2 ± 5.0yrs), young physically inactive (YPI, n = 14; 24.9 ± 4.7yrs), older physically active (OPA, n = 14; 71.2 ± 4.4yrs) or older physically inactive (OPI, n = 17; 71.0 ± 4.3yrs) groups. Both physically inactive groups (YPI and OPI) completed 12 weeks of endurance and resistance exercise. The active control groups (YPA and OPA) groups continued their normal activities. Resting blood samples were collected before (PRE) and after (POST) the intervention period. A whole blood method was used to determine lipopolysaccharide (LPS)-, peptidoglycan (PGN)-, heat shock protein 60 (HSP60)- and heat shock protein 70 (HSP70)-stimulated IL-6, TNF-α and IL-1β production. Cell-surface expression of TLR2, TLR4, and intracellular expression of IL-6 and TNF-α were measured using flow cytometry. Training increased estimated VO2max and increased strength in YPI and OPI. Serum hsCRP levels, measured using ELISA, were significantly reduced in YPI and OPI groups POST (P < 0.01); however, plasma IL-6 and IL-1β levels were unchanged. Plasma TNF-α levels were elevated in younger individuals at baseline and were increased POST. YPI and OPI had a post-training reduction in LPS-stimulated IL-6 production (P < 0.01), but LPS-stimulated IL-1β and TNF-α and PGN-stimulated cytokines were unchanged. CD14 + TLR4 expression was significantly reduced (P < 0.05) in YPI and OPI groups POST, but TLR2 was unaltered. There was a reduction in CD14+/TLR4+ intracellular expression of IL-6 and TNF-α in all groups POST (P < 0.05). This research supports the use of combined exercise training as a treatment in the reduction of inflammation. Furthermore, these results suggest that there is a training-induced lowering of TLR4 concomitant with a reduction in LPS-stimulated IL-6 production.

Degree

Ph.D.

Advisors

Flynn, Purdue University.

Subject Area

Sports medicine|Cellular biology|Nutrition|Anatomy & physiology|Animals

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