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Abstract: Toll-like receptor (TLR) agonists, ubiquitously present in the environment, are key players in activating synthesis of cytokines and chemokines that control normal and pathophysiological processes, including multiple inflammatory diseases. [...]

Abstract: Human metapneumovirus and respiratory syncytial virus are RNA viruses associated with lower respiratory tract infections. Regular symptomatic re-infection and sequelae are common, particularly in individuals with pre-existing respiratory diseases, [...]

Dietary phytosterols significantly reduce atherosclerosis in apo E-deficient mice. Because atherosclerosis is a chronic inflammatory disease, we investigated whether the antiatherogenic effects of phytosterols are associated with reductions in proinflammatory cytokine production as well as the effect of this diet on global immunocompetence. Apolipoprotein (apo) E-deficient mice were fed a cholesterol-supplemented diet in the presence or absence of 2% dietary phytosterols for 14 wk and then immunized with ovalbumin. The relations between plasma lipid concentrations, atherosclerotic lesions, and cytokine production and proinflammatory stimuli or foreign antigens were characterized. Phytosterol-enriched diets were strongly associated with reduced plasma cholesterol concentrations and atherosclerosis in conjunction with higher anti-inflammatory [interleukin (IL)-10] and lower proinflammatory cytokine [IL-6, tumor necrosis factor (TNF)-[alpha]] production. In contrast, development of cytokine and chemokine responses to ovalbumin was as strong as or even improved in the phytosterol-treated mice relative to controls. The antiatherogenic effects of dietary phytosterols in apo E-knockout mice were associated with beneficial alterations in both lipoprotein metabolism and inflammatory pathways. Decreased capacity to mount proinflammatory cytokine and chemokine responses to inflammatory stimuli did not interfere with the global immunocompetence of such mice. Thus, the desirable suppression of proinflammatory cytokine production that was associated with inhibition of atherogenesis did not impair the capacity to mount responses to foreign antigens. KEY WORDS: * proinflammatory cytokines * Thl/Th2 * immunocompetence * atherosclerosis * phytosterols

Abstract Background Psoriasin has been identified as a gene that is highly expressed in pre-invasive breast cancer, but is often downregulated with breast cancer progression. It is currently unknown whether psoriasin influences epithelial cell malignancy directly or by affecting the surrounding environment. However the protein is found in the nucleus, cytoplasm as well as extracellularly. In the present study we have sought to identify potential psoriasin-binding proteins and to describe their expression profile in breast tumors. Methods The yeast two-hybrid method was used to identify potential binding partners for psoriasin. The interaction of psoriasin with RanBPM was confirmed in-vitro by co-immunoprecipitation. The expression of RanBPM and psoriasin was measured by RT-PCR in a series of breast cell lines, breast tumors and primary lymphocytes. Results We have identified RanBPM as an interacting protein by the yeast two-hybrid assay and confirmed this interaction in-vitro by co-immunoprecipitation. RT-PCR analysis of RanBPM mRNA expression in cell lines (n = 13) shows that RanBPM is widely expressed in different cell types and that expression is higher in tumor than in normal breast epithelial cell lines. RanBPM expression can also be induced in peripheral blood mononuclear cells by treatment with PHA. RanBPM mRNA is also frequently expressed in invasive breast carcinomas (n = 64) and a higher psoriasin/RanBPM ratio is associated with both ER negative (p < 0.0001) and PR negative status (p < 0.001), and inflammatory cell infiltrates (p < 0.0001) within the tumor. Conclusions These findings support the hypothesis that psoriasin may interact with RanBPM and this may influence both epithelial and stromal cells and thus contribute to breast tumor progression.

Changes in maternal innate immunity during healthy human pregnancy are not well understood. Whether basal immune status in vivo is largely unaffected by pregnancy, is constitutively biased towards an inflammatory phenotype (transiently enhancing host defense) or exhibits anti-inflammatory bias (reducing potential responsiveness to the fetus) is unclear. Here, in a longitudinal study of healthy women who gave birth to healthy infants following uncomplicated pregnancies within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, we test the hypothesis that a progressively altered bias in resting innate immune status develops. Women were examined during pregnancy and again, one and/or three years postpartum. Most pro-inflammatory cytokine expression, including CCL2, CXCL10, IL-18 and TNFα, was reduced in vivo during pregnancy (20–57%, p<0.0001). Anti-inflammatory biomarkers (sTNF-RI, sTNF-RII, and IL-1Ra) were elevated by ~50–100% (p<0.0001). Systemic IL-10 levels were unaltered during vs. post-pregnancy. Kinetic studies demonstrate that while decreased pro-inflammatory biomarker expression (CCL2, CXCL10, IL-18, and TNFα) was constant, anti-inflammatory expression increased progressively with increasing gestational age (p<0.0001). We conclude that healthy resting maternal immune status is characterized by an increasingly pronounced bias towards a systemic anti-inflammatory innate phenotype during the last two trimesters of pregnancy. This is resolved by one year postpartum in the absence of repeat pregnancy. The findings provide enhanced understanding of immunological changes that occur in vivo during healthy human pregnancy. [ABSTRACT FROM AUTHOR]