Effect of cell-surface components and metabolites of lactic acid bacteria and probiotic organisms on cytokine production and induction of CD25 expression in human peripheral mononuclear cells

In the current study, the relative contribution of cell-surface components (CSC) and cell-free supernatants (CFS) in the immuno-modulatory properties of 17 strains of probiotic and lactic acid bacteria (LAB) was assessed. The production of pro- and antiinflammatory cytokines including IL-2, IL-4, IL-10, IL-12 p70, IFN-γ, tumor necrosis factor-α (TNF-α), and transforming growth factor-β was measured at different time points after stimulation of buffy coat derived-peripheral blood mononuclear cells (PBMC) from healthy donors with CSC and CFS of probiotic and LAB. Results showed that CSC of probiotic and LAB strains induced production of T helper 1 and 2 type cytokines. Transforming growth factor-β was stimulated at highest concentrations, followed by IL-10 and TNF-α. The CFS of all tested bacterial strains induced PBMC for significantly high levels of IL-10 secretion compared with unstimulated cells, but the values were less than lipopolysaccharide-stimulated cells. Cytokines due to CFS stimulation showed declined concentration for IL-2, TNF-α, and IL-4, and complete disappearance of IL-12, IFN-γ, and transforming growth factor-β in the cultured medium at 96 h of incubation. Results of cytokine data demonstrate proinflammatory TNF-α immune responses are mainly directed through cell-surface structures of probiotic and LAB, but antiinflammatory immune responses are mediated both by metabolites and cell-surfaces of these bacteria. The induction of CD4(+)CD25(+) regulatory T cells after stimulation of PBMC with CSC and CFS of probiotic and LAB showed regulatory T cell activity appeared to be influenced both by the CSC and metabolites, but was principally triggered by cell surfaces of probiotic and LAB strains.

Inhibition of reactive oxygen species production ameliorates inflammation induced by influenza A viruses via upregulation of SOCS1 and SOCS3.

Highly pathogenic avian influenza virus infection is associated with severe mortality in both humans and poultry. The mechanisms of disease pathogenesis and immunity are poorly understood although recent evidence suggests that cytokine/chemokine dysregulation contributes to disease severity following H5N1 infection. Influenza A virus infection causes a rapid influx of inflammatory cells, resulting in increased reactive oxygen species production, cytokine expression, and acute lung injury. Proinflammatory stimuli are known to induce intracellular reactive oxygen species by activating NADPH oxidase activity. We therefore hypothesized that inhibition of this activity would restore host cytokine homeostasis following avian influenza virus infection. A panel of airway epithelial and immune cells from mammalian and avian species were infected with A/Puerto Rico/8/1934 H1N1 virus, low-pathogenicity avian influenza H5N3 virus (A/duck/Victoria/0305-2/2012), highly pathogenic avian influenza H5N1 virus (A/chicken/Vietnam/0008/2004), or low-pathogenicity avian influenza H7N9 virus (A/Anhui/1/2013). Quantitative real-time reverse transcriptase PCR showed that H5N1 and H7N9 viruses significantly stimulated cytokine (interleukin-6, beta interferon, CXCL10, and CCL5) production. Among the influenza-induced cytokines, CCL5 was identified as a potential marker for overactive immunity. Apocynin, a Nox2 inhibitor, inhibited influenza-induced cytokines and reactive oxygen species production, although viral replication was not significantly altered in vitro. Interestingly, apocynin treatment significantly increased influenza virus-induced mRNA and protein expression of SOCS1 and SOCS3, enhancing negative regulation of cytokine signaling. These findings suggest that apocynin or its derivatives (targeting host responses) could be used in combination with antiviral strategies (targeting viruses) as therapeutic agents to ameliorate disease severity in susceptible species.

Innate immunity in the mammary gland and the role of the milk peptidome

 This research investigated how the mammary gland responds to disease states such as mastitis and how the milk plays a protective role. An in vitro mammary model was developed and shown to replicate the same responses to the breast when challenged with bacterial proteins demonstrating the usefulness of this model for future investigation of therapeutic interventions.

The effects of bed-rest and countermeasure exercise on the endocrine system in male adults: evidence for immobilization-induced reduction in sex hormone-binding globulin levels

BACKGROUND AND AIM: There is limited data on the effects of inactivity (prolonged bed-rest) on parameters of endocrine and metabolic function; we therefore aimed to examine changes in these systems during and after prolonged (56- day) bed-rest in male adults. SUBJECTS AND METHODS: Twenty healthy male subjects underwent 8 weeks of strict bed-rest and 12 months of follow-up as part of the Berlin Bed Rest Study. Subjects were randomized to an inactive group or a group that performed resistive vibration exercise (RVE) during bed-rest. All outcome parameters were measured before, during and after bed-rest. These included body composition (by whole body dual X-ray absorptiometry), SHBG, testosterone (T), estradiol (E2), PRL, cortisol (C), TSH and free T3 (FT3). RESULTS: Serum SHBG levels decreased in inactive subjects but remained unchanged in the RVE group (p<0.001). Serum T concentrations increased during the first 3 weeks of bed-rest in both groups (p<0.0001), while E2 levels sharply rose with re-mobilization (p<0.0001). Serum PRL decreased in the control group but increased in the RVE group (p=0.021). C levels did not change over time (p≥0.10). TSH increased whilst FT3 decreased during bed-rest (p all ≤0.0013). CONCLUSIONS: Prolonged bed-rest has significant effects on parameters of endocrine and metabolic function, some of which are related to, or counteracted by physical activity.

Signaling via the CytoR/JAK/STAT/SOCS pathway: emergence during evolution

Cell-cell signaling represents an essential hallmark of multicellular organisms, which necessarily require a means of communicating between different cell populations, particularly immune cells. Cytokine receptor signaling through the Janus kinase/Signal Transducer and Activator of Transcription/Suppressor of Cytokine Signaling (CytoR/JAK/STAT/SOCS) pathway embodies one important paradigm by which this is achieved. This pathway has been extensively studied in vertebrates and protostomes and shown to play fundamental roles in development and function of immune and other cells. However, our understanding of the origins of the individual pathway components and their assembly into a functional pathway has remained limited. This study examined the origins of each component of this pathway through bioinformatics analysis of key extant species. This has revealed step-wise accretion of individual components over a large evolutionary time-frame, but only in bilateria did a series of innovations allow their final coalescence to form a complete pathway. Assembly of the CytoR/JAK/STAT pathway has followed the retrograde model of pathway evolution, whereas addition of the SOCS component has adhered to the patchwork model.