Stress-induced enhancement of NF-kappaB DNA-binding in the peripheral blood leukocyte pool: effects of lymphocyte redistribution.
To identify signaling pathways by which the sympathetic nervous system (SNS) might alter gene expression in the immune system, we assayed activation of the inflammatory transcription factor NF-kappaB in peripheral blood mononuclear cells (PBMC) from 13 healthy young adults at rest and following 5 min of intense exercise. SNS activation was verified by changes in cardiovascular parameters and mobilization of NK cells into circulating blood. Electrophoretic mobility shift assays (EMSA) of nuclear protein extracts confirmed previous findings that SNS activation increased NF-kappaB DNA-binding activity in bulk PBMC. However, analyses of isolated leukocyte subsets failed to indicate any increase on a per-cell basis in NK cells (the major carriers of NF-kappaB activity in circulating PBMC), in the residual CD56- leukocyte pool, or in CD14+ monocytes. Regression analyses indicated a strong correlation between increasing NK cell prevalence and changes in NF-kappaB DNA-binding activity in bulk PBMC, and suggested that no change in EMSA activity would be observed in the absence of NK cell mobilization. Such results imply that SNS-induced mobilization of NK cells can rapidly (< 10 min) alter NF-kappaB DNA-binding activity in the circulating PBMC pool without generating any true change in NF-kappaB activity on a per-cell basis. Implications for future efforts to analyze stress effects on leukocyte gene expression are considered.
Richlin
Vanessa A
VA
Case Western Reserve School of Medicine, Los Angeles, CA 90095-1678, USA.
Arevalo
Jesusa M G
JM
Zack
Jerome A
JA
Cole
Steve W
SW
D000222:Adaptation, Physiological; D000293:Adolescent; D000328:Adult; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007962:Leukocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008297:Male; D016260:Monocytes, Activated Killer / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009434:Neural Pathways / Q000276:immunology; D015213:Neuroimmunomodulation / Q000235:genetics; D012016:Reference Values; D013312:Stress, Physiological / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000276:immunology
D019002:CD56 Antigen; D018950:Lipopolysaccharide Receptors; D016328:NF-kappa B; D004247:DNA