Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise.
While exercise effects on the immune system have received increasing attention in recent years, it remains unclear to what extent gender and fluctuations in sex hormones during menstrual cycle influence immunological responses to exercise.



We investigated mRNA changes induced through exhaustive exercise (half-marathon; pre-exercise and post-exercise [30 min, 3 h, 24 h] on whole blood cultures ± lipopolysaccharide [LPS] [1 h]) with a specific focus on sex differences (men vs women in luteal phase) as an extension of our previous study.



Inflammation related signaling pathways, TLRs, cytosolic DNA sensing and RIG-I like receptors were differentially activated between sexes in LPS-stimulated cultures. Genes differentially regulated between sexes included TNIP-1, TNIP-3, IL-6, HIVEP1, CXCL3, CCR3, IL-8, and CD69, revealing a bias towards less anti-inflammatory gene regulation in women compared to men. In addition, several genes relevant to brain function (KMO, DDIT4, VEGFA, IGF1R, IGF2R, and FGD4) showed differential activation between sexes. Some of these genes (e.g., KMO in women, DDIT4 in both sexes) potentially constitute neuroprotective mechanisms.



These data reveal that the exercise-induced change in gene expression might be gender and menstrual cycle phase dependent.
Institute for Memory Impairments and Neurological Disorders (MIND Institute), University of California-Irvine (UCI), Irvine, CA, USA. asghaa1@uci.edu.|Institute for Memory Impairments and Neurological Disorders (MIND Institute), Gillespie Neuroscience Research Facility, 1113, University of California, Irvine, 92697.4540, USA. asghaa1@uci.edu.
Asghar
A
Abbasi
Laboratory of Pulmonary and Exercise Immunology (LABPEI), Nove de Julho University (UNINOVE), Sao Paulo, Brazil.
Rodolfo
R
de Paula Vieira
Hertie Institute for Clinical Brain Research and Center of Neurology, University Hospital Tuebingen, Tuebingen, Germany.
Felix
F
Bischof
Agilent Technologies Sales and Services, GmbH & Co. KG, Hewlett-Packard-Strasse 8, 76337, Waldbronn, Germany.
Michael
M
Walter
Department of Pathology and Laboratory Medicine, University of California-Los Angeles (UCLA), Los Angeles, CA, USA.
Masoud
M
Movassaghi
Institute for Memory Impairments and Neurological Disorders (MIND Institute), University of California-Irvine (UCI), Irvine, CA, USA.
Nicole C
NC
Berchtold
Department of Sports Medicine, University Hospital Tuebingen, Tuebingen, Germany.
Andreas M
AM
Niess
Institute for Memory Impairments and Neurological Disorders (MIND Institute), University of California-Irvine (UCI), Irvine, CA, USA.
Carl W
CW
Cotman
Zentrum für Klinische Transfusionsmedizin (ZKT) and Institute of Clinical and Experimental Transfusion Medicine (IKET), University Hospital Tuebingen, Tuebingen, Germany.
Hinnak
H
Northoff
D000328:Adult; D000886:Anthropometry; D056352:Athletes; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D015444:Exercise; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006728:Hormones; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008597:Menstrual Cycle / Q000502:physiology; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
D016207:Cytokines; D004731:Endotoxins; D006728:Hormones; D008070:Lipopolysaccharides
Exercise; Inflammatory genes; LPS stimulation; Sex differences; Toll-like receptors