Genetic prescription for health: The impact of exercise and inflammation on immunugenetics

While inflammation is a central part of our immune defense, excessive inflammation in acute and chronic situations (sepsis; inflammaging) can be very harmful and life shortening. Exercise has been shown to induce and modify gene expression in different tissues. Among the genes strongly activated by exercise, inflammation-related genes are of prime importance. We try to give an overview about the effect of exercise on the activation of genes and pathways involved in inflammation. Activation of inflammatory genes can readily be observed in the muscle, where exercise begins. Other organs can also be influenced by exercise, such as brain, liver and heart, but a mirror of inflammatory regulations by exercise can be found in peripheral blood. The majority of investigations, including ours, thus, have used peripheral blood for analysis. With the advent of microarray technology enormous amounts of data on gene expression following exercise have been generated and a large part of these is related to inflammation. Altogether, it seems that exercise induces both, pro-inflammatory genes (including asthma related genes) but also prominent anti-inflammatory genes. There are differences in gene regulation due to type and duration of exercise, sex and age of the subjects, and the technologies used for analysis. Observations of exercise activity in athletes with solid transplants who are under immunosuppressive medication shows that the vast part of the inflammatory reaction and its anti-inflammatory counter reaction are absent in these patients in spite of performance comparable to healthy subjects. We also present results from a recent study which includes ex vivo stimulation by endotoxin (LPS). They show that exercise can also modify the reaction of peripheral blood cells to TLRs mediated pathogen activation. In special, activation of TNIP3, a negative regulator of TLRs signaling and down-regulation of IFN-β1 through exercise could be observed in these cultures but not in unstimulated cultures. A hypothesis of the interaction of exercise with TLRs signaling will be presented

Genetic Fingerprint of Immunosuppression Following Half-marathon Running in Microarray Study

ABSTRACT Introduction: An acute bout of exhaustive exercise such as marathon or half-marathon running can interfere with immunity, reflected by transient immunosuppression and inflammation like reaction following the event. To gain more insights into these mechanisms, the capacity of whole blood cultures in profiling gene expression in response to endotoxin (LPS) was studied in athletes before, 30min after, 3h after and 24h after a half-marathon run. Methods: Four well trained men and 4 well trained women participated and gene expression patterns were assessed in LPS-stimulated (1h) and unstimulated whole blood using Affymetrix GeneChip microarrays. Results: exercise significantly altered several genes in LPS-stimualted and unstimulated blood cultures of male and female athletes. A row of genes with prominent anti-inflammatory function were strongly up-regulated in unstimulated cultures in both sexes (ARG-1, SOCS3, DUSP-1, BMX, GOS2, CD177, and GJB6). In the same cultures a row of highly inflammatory and apoptotic genes were down-regulated (Granzymes A-M-B-K-H, PRF1, SPON2, Granulysin, KLRF1, PLEKHF1). Some of these genes which were significantly up-or down-regulated in unstimulated cultures were also strongly regulated in LPS-stimulated cultures (GJB6, ARG-1, ORM2, KLRF1, TRA@///TRD@, Granzymes, SPON2). In addition, there were some strongly regulated genes which could only be detected in LPS-stimulated cultures but not in unstimulated cultures. Among these, TNIP3, PLAU, HIVEP1, and SLED were up-regulated and IFN-β, IFN-γ, L-12B, CXCL4. CXCL10 and TRAF1 were significantly down-regulated. Conclusion: there is a row of genes which are strongly regulated through exercise but can only be detected in (endotoxin) stimulated cultures. This is direct evidence showing that the response to pathogens is strongly down-regulated following prolonged exhaustive exercise through different ways

Good Feasibility of the New German Blood Donor Questionnaire

Background: We assessed the effect of the uniform donor questionnaire (UDQ) on deferral rates in first-time and repeat donors. We focused on the introduced question about unprotected sexual contact with a new partner. Another goal was a stratified comparison of the deferral rates of the donor questionnaire (DQ) and UDQ. Methods: Data on donors and deferrals using the DQ and UDQ were collected at four blood establishments. The comparison included a 2-year period by questionnaire version. For the comparison of the questionnaires, an adjusted multinomial logistic regression was performed. Results: The analysis included 260,848 donations. First-time (FTD) and repeat donations (RD) showed higher deferral rates with the UDQ (FTD +5.4%, RD +1.4%). Deferral due to a new partner was 3.0% in first-time and 0.4% in repeat donors. The majority of these occurred in the youngest age groups. The most frequent deferral criterion was ‘disease' (5.1%). Conclusion: The regression revealed stronger predictors for deferral than the questionnaire version. Especially younger age carried a higher and independent risk for deferral. The additional deferrals of mainly young first-time donors due to a new sexual partner may identify those donors with potential heterosexual risk behavior who would otherwise not be identified

Aerobic exercise inhibits acute lung injury: from mouse to human evidence Exercise reduced lung injury markers in mouse and in cells

Acute respiratory distress syndrome (ARDS) is defined as hypoxemic respiratory failure with intense pulmonary inflammation, involving hyperactivation of endothelial cells and neutrophils. Given the anti-inflammatory effects of aerobic exercise (AE), this study investigated whether AE performed daily for 5 weeks would inhibit extra-pulmonary LPS-induced ARDS. C57Bl/6 mice were distributed into Control, Exercise, LPS and Exercise+ LPS groups. AE was performed on a treadmill for 5x/week for four weeks before LPS administration. 24hours after the final AE physical test, animals received 100ug of LPS intra-peritoneally. In addition, whole blood cell culture, neutrophils and human endothelial cells were pre-incubated with IL-10, an anti-inflammatory cytokine induced by exercise. AE reduced total protein levels (p<0.01) and neutrophil accumulation in bronchoalveolar lavage (BAL) (p<0.01) and lung parenchyma (p<0.01). AE reduced BAL inflammatory cytokines IL-1 beta, IL-6 and GM-CSF (p<0.001), CXCL1/KC, IL-17, TNF-alpha and IGF-1 (p<0.01). Systemically, AE reduced IL-1 beta, IL-6 and IFN-gamma (p<0.001), CXCL1/KC (p<0.01) and TNF-alpha (p<0.05). AE increased IL-10 levels in serum (p<0.001) and BAL (p<0.001). Furthermore, AE increased superoxide dismutase SOD (p<0.01) and decreased superoxide anion accumulation in the lungs (p<0.01). Lastly, pre-incubation with IL-10 significantly reduced LPS-induced activation of whole blood cells, neutrophils and HUVECs, as observed by reduced production of IL-1 beta, IL-6, IL-8 and TNF-alpha. Our data suggest that AE inhibited LPS-induced lung inflammation by attenuating inflammatory cytokines and oxidative stress markers in mice and human cell culture via enhanced IL-10 production.Sao Paulo Research Foundation (FAPESP) [2012/15165-2]Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) [311335-2015-2]Comissao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [12804/13-4, 1303/13-9]FAPESP [2013/24076-6, 2014/23196-0, 2012/14604-8, 2012/25435-7, 2012/24880-7]CAPESNove Julho Univ, Sao Paulo, SP, BrazilBrazilian Inst Teaching & Res Pulm & Exercise Imm, Sao Jose Dos Campos, SP, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, SP, BrazilUniv Brasil, Sao Paulo, SP, BrazilUniv Sao Paulo, Sch Med, Dept Pathol LIM 59, Sao Paulo, SP, BrazilUniv Fed Lavras UFLA, Sci Dept Hlth, Lavras, MG, BrazilFed Univ Sao Paulo UNIFESP, Campus Sao Paulo, Sao Paulo, SP, BrazilHarbor UCLA Med Ctr, Div Resp & Crit Care Physiol & Med, Los Angeles Biomed Res Inst, Torrance, CA 90509 USAUniv Tubingen, Inst Clin & Expt Transfus Med IKET, Tubingen, GermanyFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, Campus Sao Paulo, Sao Paulo, SP, BrazilFAPESP [2012/15165-2]CNPq [311335-2015-2]CAPES [12804/13-4, 1303/13-9]FAPESP [2013/24076-6, 2014/23196-0, 2012/14604-8, 2012/25435-7, 2012/24880-7]Web of Scienc

NCO-sP(EO-stat-PO) Coatings on Gold Sensors—a QCM Study of Hemocompatibility

The reliability of implantable blood sensors is often hampered by unspecific adsorption of plasma proteins and blood cells. This not only leads to a loss of sensor signal over time, but can also result in undesired host vs. graft reactions. Within this study we evaluated the hemocompatibility of isocyanate conjugated star shaped polytheylene oxide—polypropylene oxide co-polymers NCO-sP(EO-stat-PO) when applied to gold surfaces as an auspicious coating material for gold sputtered blood contacting sensors. Quartz crystal microbalance (QCM) sensors were coated with ultrathin NCO-sP(EO-stat-PO) films and compared with uncoated gold sensors. Protein resistance was assessed by QCM measurements with fibrinogen solution and platelet poor plasma (PPP), followed by quantification of fibrinogen adsorption. Hemocompatibility was tested by incubation with human platelet rich plasma (PRP). Thrombin antithrombin-III complex (TAT), β-thromboglobulin (β-TG) and platelet factor 4 (PF4) were used as coagulation activation markers. Furthermore, scanning electron microscopy (SEM) was used to visualize platelet adhesion to the sensor surfaces. Compared to uncoated gold sensors, NCO-sP(EO-stat-PO) coated sensors revealed significant better resistance against protein adsorption, lower TAT generation and a lower amount of adherent platelets. Moreover, coating with ultrathin NCO-sP(EO-stat-PO) films creates a cell resistant hemocompatible surface on gold that increases the chance of prolonged sensor functionality and can easily be modified with specific receptor molecules