How to deal with COVID-19 epidemic-related lockdown physical inactivity and sedentary increase in youth? Adaptation of Anses' benchmarks.

Faced with the spread of the SARS-CoV-2 virus, regulatory measures aiming to prevent interpersonal contaminations have been undertaken and among these, lockdown. Due to strong restrictions out-of-home movements, we hypothesize that overall physical activity will decrease and sedentary behavior increase. This could result in highest exposure to the well-known risk related to insufficient physical activity. To mitigate physical inactivity and sedentary behaviors health-related risks related to children and adolescents lockdown and school closure, Anses (French Agency for Food, Environmental and Occupational Health & Safety) has adapted, within the first days of the public authorities' prescription, its former benchmarks. This paper supports and comments Anses' Opinion by raising the questions of whether, why, and how to deal with short- or medium-term lockdown-related physical inactivity and sedentary behavior increases. Short-term and unknown long term-impacts on mental health and well-being, physical fitness and eating behaviors clearly appearing for children and adolescents as being the main issues of concern are highlighted. Targeting the compensations of the physical inactivity increase, the types, frequencies and durations of physical activity, are adapted to restricted environment. Sedentary behavior limitation and frequent interruptions becomes a priority. Overall, considering children and adolescents, the emerging risk justifies proposing specific adaptations and type of activities in order to ensure maintaining health underpinned, at least partly, by physiological equilibrium and physical fitness and avoid the installation of new unhealthy habits or routines that young people could keep after lockdown.

Secretory component is cleaved by neutrophil serine proteinases but its epithelial production is increased by neutrophils through NF-kappa B- and p38 mitogen-activated protein kinase-dependent mechanisms.

We previously showed that expression of polymeric immunoglobulin receptor (pIgR)/secretory component (SC), the epithelial receptor assuming transport of polymeric IgA in mucosal secretions, is strongly decreased in severe chronic obstructive pulmonary disease. Here, we evaluated in vitro the effects of polymorphonuclear neutrophil (PMN) mediators on pIgR/SC. On polyacrylamide gel electrophoresis analysis, soluble SC was rapidly cleaved by supernatants from phorbol-myristate-acetate-activated PMN, through a serine proteinase activity. Moreover, purified PMN serine proteinases also cleaved SC. Similarly, polymeric IgA was rapidly cleaved in monomers by neutrophil elastase, whereas secretory immunoglobulin A was relatively resistant to neutrophil elastase. Surface pIgR on human bronchial epithelial cells was also cleaved by serine proteinases, as shown by immunofluorescence. In contrast, pIgR/SC production by cultured epithelial cells (quantified by enzyme-linked immunosorbent assay) was significantly increased by supernatants from interleukin-8/formylmethionylleucylphenylalanine-activated PMN (122.6 +/- 17.3 versus 70.9 +/- 9 ng/mg protein, P < 0.01). Upregulation of pIgR/SC production by bronchial epithelial cells was abolished by nuclear factor kappa B- and p38 mitogen-activated protein kinase (MAPK) inhibitors. Moreover, supernatants from interleukin-8/formylmethionylleucylphenylalanine-activated PMN induced the phosphorylation of I kappa B-alpha and p38 MAPK in epithelial cells, independently of serine proteinases. Thus, PMN serine proteinases cleave pIgR/SC, whereas activated PMN induce an increased pIgR/SC expression through epithelial activation of nuclear factor kappa B and p38 MAPK pathways.

IL-9 inhibits oxidative burst and TNF-alpha release in lipopolysaccharide-stimulated human monocytes through TGF-beta.

IL-9 is a Th2 cytokine that exerts pleiotropic activities on T cells, B cells, mast cells, hematopoietic progenitors, and lung epithelial cells, but no effect of this cytokine has been reported so far on mononuclear phagocytes. Human blood monocytes preincubated with IL-9 for 24 h before LPS or PMA stimulation exhibited a decreased oxidative burst, even in the presence of IFN-gamma. The inhibitory effect of IL-9 was specifically abolished by anti-hIL-9R mAb, and the presence of IL-9 receptors was demonstrated on human blood monocytes by FACS. IL-9 also down-regulated TNF-alpha and IL-10 release by LPS-stimulated monocytes. In addition, IL-9 strongly up-regulated the production of TGF-beta1 by LPS-stimulated monocytes. The suppressive effect of IL-9 on the respiratory burst and TNF-alpha production in LPS-stimulated monocytes was significantly inhibited by anti-TGF-beta1, but not by anti-IL-10Rbeta mAb. Furthermore, IL-9 inhibited LPS-induced activation of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases in monocytes through a TGF-beta-mediated induction of protein phosphatase activity. In contrast, IL-4, which exerts a similar inhibitory effect on the oxidative burst and TNF-alpha release by monocytes, acts primarily through a down-regulation of LPS receptors. Thus, IL-9 deactivates LPS-stimulated blood mononuclear phagocytes, and the mechanism of inhibition involves the potentiation of TGF-beta1 production and extracellular signal-regulated kinase inhibition. These findings highlight a new target cell for IL-9 and may account for the beneficial activity of IL-9 in animal models of exaggerated inflammatory response.

Effect of IgA on respiratory burst and cytokine release by human alveolar macrophages: role of ERK1/2 mitogen-activated protein kinases and NF-kappaB.

Human alveolar macrophages (HAM) express FcalphaR receptors for immunoglobulin (Ig)A which could link humoral and cellular branches of lung immunity. Here, we investigate the effects of polymeric (p-IgA) and secretory (S-IgA) IgA interaction with Fc(alpha)R on lipopolysaccharide (LPS)- and phorbol myristate acetate (PMA)-activated respiratory burst and TNF-alpha release by HAM. Activation of HAM with LPS and PMA increases the respiratory burst and TNF-alpha release through activation of the extracellular signal-related protein kinases 1 and 2 (ERK1/2) pathway, because these effects are inhibited by treatment of HAM with PD98059, a selective inhibitor of mitogen-activated protein (MAP)/ERK kinases (MEK) pathway. S-IgA and p-IgA downregulate the LPS-increased respiratory burst in HAM through an inhibition of ERK1/2 activity. In contrast, p- and S-IgA induce an increase in the respiratory burst of PMA-treated HAM. This effect is associated with an upregulation by IgA of the PMA-induced phosphorylation of ERK1/2 and is also inhibited by PD98059. Moreover, p-IgA and S-IgA enhance TNF-alpha release by HAM through an alternative pathway distinct from ERK1/2. Because LPS is known to activate nuclear factor-kappaB (NF-kappaB) in HAM, we evaluate the effect of IgA on NF-kappaB. Treatment of HAM with LPS, p- and S-IgA, but not PMA, induces NF-kappaB activation through IkappaBalpha phosphorylation and subsequent proteolysis. Antioxidants, namely N-acetylcysteine (NAC) and glutathione (GSH), have no effects on IgA-mediated NF-kappaB nuclear translocation and only a minor and late effect on that of LPS, suggesting that reactive oxygen intermediates (ROI) play a minor role in HAM activation through NF-kappaB. TNF-alpha release by LPS-activated HAM is sensitive to NF-kappaB inhibition and only partly to oxidant scavenging. In contrast, TNF-alpha release by IgA-treated HAM is not dependent on oxidants and only partly dependent on NF-kappaB. Our results show a differential HAM regulation by IgA through both dependent and independent modulation of ERK pathway. In addition, IgA activates NF-kappaB and this effect was independent on oxidants. These data may help to understand the role of IgA in both lung protection and inflammation.

Phagocytosis and killing of intracellular pathogens: interaction between cytokines and antibiotics.

Phagocytosis and bacterial killing are the primary functions of macrophages. Among the mechanisms involved in the phagocytic process, cytokines, especially those of T-helper 1 profile, appear to influence considerably the internalization and the intracellular fate of the pathogen within the macrophage. In particular, the evidence for a cooperation of cytokines with antibiotics in intracellular infection could provide new therapeutic approaches to intracellular infectious diseases in the future.