Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These data reveal that the exercise-induced change in gene expression might be gender and menstrual cycle phase dependent. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0758-5) contains supplementary material, which is available to authorized users

Assessment of dietary fat intake and innate immune activation as risk factors for impaired lung function

Background/objectives: Preservation of lung health with aging is an important health issue in the general population, as loss of lung function with aging can lead to the development of obstructive lung disease and is a predictor of all-cause and cardiovascular mortality. Inflammation is increasingly linked to loss of lung function and evidence suggests that consumption of dietary fat exacerbates inflammation. We aimed to determine the association between dietary fat intake and lung function in older people. Subjects/methods: Participants from the Hunter community study, a population-based cohort, were recruited during 2004 and 2005. Participants received a clinical assessment, including spirometry, and provided a blood sample. Diets were analyzed using food-frequency questionnaires. Plasma interleukin (IL)-6 and C-reactive protein was measured by Enzyme-Linked immunosorbent assay. Results: Using backward stepwise linear regression, %energy from dietary fat, age and plasma IL-6 were considered as negative predictors of forced expiratory volume in one second (FEV₁) in men. Also in men, %energy intake from dietary fat, age, body mass index and IL-6 were negative predictors of %predicted forced vital capacity (FVC). Smoking and age were negative predictors of FEV₁/FVC. In women, plasma IL-6 and age were negative predictors of %FVC, whereas obesity was positively associated with FEV₁/FVC. Conclusions: An increased proportion of fat in the diet is associated with the reduced lung function in older men. Dietary-fat induced innate immune activation and IL-6 release may contribute to this effect. Dietary interventions involving fat restriction should be further investigated as means of preserving lung function with aging