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Conducting Maximal and Submaximal Endurance Exercise Testing to Measure Physiological and Biological Responses to Acute Exercise in Humans
Published on: October 17, 2018
Maximal Exercise Alters the Inflammatory Phenotype and Response of Mononuclear Cells
Aaron L Slusher1, Tiffany M Zúñiga, Edmund O Acevedo
1Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, VA.
Purpose:
Monocytes express the CD14 receptor that facilitates lipopolysaccharide (LPS) ligation to toll-like receptor 4 (TLR4) to elicit production of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α). However, proinflammatory conditions, such as strenuous exercise, increase the percentage of monocytes expressing CD16, a receptor that enhances LPS stimulated TNF-α production. Therefore, we examined whether maximal treadmill exercise would alter the inflammatory phenotype of classical (CD14/CD16) and proinflammatory monocytes (intermediate [CD14/CD16] and nonclassical [CD14/CD16]), evidenced by changes in TLR4, CD14, and CD16 receptor expression, and their inflammatory response to ex vivo LPS stimulation.
Methods:
Human mononuclear cells from 25 male participants (age, 24.2 ± 4.0 yr) were isolated before and after exercise to assess TLR4, CD14, and CD16 expression by flow cytometry and ex vivo production of LPS-stimulated inflammatory cytokines (IL-6, IL-10, and TNF-α).
Results:
Exercise reduced the percentage of classical monocytes and increased the percentage of intermediate and nonclassical monocytes. In addition, TLR4 expression decreased on classical and intermediate monocytes, but not the nonclassical monocyte subset. Furthermore, although CD14 expression decreased on all monocyte subsets, CD16 expression increased on intermediate monocytes only. In parallel with these phenotypic changes, the inflammatory milieu shifted toward a proinflammatory response after LPS stimulation (decreased IL-6 and IL-10 and increased IL-6 to IL-10 ratio and TNF-α production).
Conclusions:
These findings demonstrate that acute maximal exercise elicits a proinflammatory phenotype of isolated monocytes exposed to LPS and highlight potential mechanisms that will help elucidate the role of acute and chronic exercise on the innate immune response of circulating monocytes.
Insights
Maximal exercise promotes a proinflammatory monocyte phenotype, altering receptor expression and inflammatory cytokine production. This shift impacts the innate immune response, influencing how monocytes react to lipopolysaccharide (LPS).
Area of Science:
- Immunology
- Exercise Physiology
Background:
- Monocytes play a key role in innate immunity, expressing CD14 and toll-like receptor 4 (TLR4) for lipopolysaccharide (LPS) recognition.
- Proinflammatory states, like strenuous exercise, can alter monocyte subset percentages and receptor expression (CD16), potentially enhancing inflammatory responses.
Purpose of the Study:
- To investigate the impact of maximal treadmill exercise on monocyte inflammatory phenotype.
- To examine changes in TLR4, CD14, and CD16 expression on classical, intermediate, and nonclassical monocytes post-exercise.
- To assess the ex vivo inflammatory response of monocytes to LPS stimulation after exercise.
Main Methods:
- Human peripheral blood mononuclear cells were isolated from 25 male participants before and after maximal exercise.
- Flow cytometry was used to quantify TLR4, CD14, and CD16 expression on monocyte subsets.
- Ex vivo LPS stimulation assessed the production of inflammatory cytokines (IL-6, IL-10, TNF-α).
Main Results:
- Maximal exercise decreased classical monocytes and increased intermediate and nonclassical monocytes.
- TLR4 expression decreased on classical and intermediate monocytes, while CD16 increased on intermediate monocytes.
- Post-exercise monocytes exhibited a proinflammatory response to LPS, with altered IL-6, IL-10, and TNF-α production.
Conclusions:
- Acute maximal exercise induces a proinflammatory phenotype in circulating monocytes.
- Changes in monocyte subset distribution and receptor expression contribute to an altered innate immune response.
- These findings provide insights into the role of exercise in modulating monocyte function and immune response.
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