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Malignant mesothelioma (MM) is a highly fatal tumor of inner body membranes, the extensive growth of which is supported by both a weak immunogenicity and the ability to reprogram surrounding immune cells towards tumor-supporting phenotypes. Interleukin-17 (IL-17) is a major inflammatory cytokine which is now accepted as the paradigmatic cytokine of many autoimmune diseases; however, its role in tumor immunology has only been partially unraveled, and no data exist regarding its possible involvement in MM. Thus, in this work we evaluated the ability of MM to induce IL-17 production in immune cells and the effects of IL-17 on MM growth and invasiveness. Our data show for the first time that macrophages and CD4+ T-cells are polarized by MM to produce IL-17, and that this cytokine exerts multiple tumor-supporting effects on both cell growth and invasiveness. These data provide novel evidence of the crosstalk occurring between MM and immune cells and suggest potential targets for the development of new pharmacological approaches for MM treatment. [ABSTRACT FROM AUTHOR]

Abstract: Brain Natriuretic Peptide (BNP), besides retaining vasodilatory, diuretic and natriuretic properties, is a vasoactive hormone that it is also involved in several cardiac diseases as well as severe sepsis and septic shock. All these conditions are characterized by an ongoing inflammatory response consisting in a complex interaction of pleiotropic mediators derived from plasma or cells, including monocytes and macrophages. However, the relationship between this hormone and inflammation remains to be elucidated. Therefore, the aim of the present study was to evaluate a possible BNP immunomodulatory activity on macrophages. Our results demonstrate that BNP regulates the production of major inflammatory molecules, such as reactive oxygen- and nitrogen species (ROS and RNS), leukotriene B4 (LTB4), prostaglandin E2 (PGE2); modulates the cytokines (TNF-α, IL-12 and IL-10) profile, and affects cell motility. These results furnish novel and brand-new proofs on BNP ability of modulating the production of inflammatory mediators in macrophages whose role has broad implications in inflammatory states where increased BNP levels have been reported. [Copyright &y& Elsevier]

Mutations in the COL13A1 gene result in congenital myasthenic syndrome type 19 (CMS19), a disease of neuromuscular synapses and including various skeletal manifestations, particularly facial dysmorphisms. The phenotypic consequences in Col13a1 null mice (Col13a1−/−) recapitulate the muscle findings of the CMS19 patients. Collagen XIII (ColXIII) is exists as two forms, a transmembrane protein and a soluble molecule. While the Col13a1−/− mice have poorly formed neuromuscular junctions, the prevention of shedding of the ColXIII ectodomain in the Col13a1tm/tm mice results in acetylcholine receptor clusters of increased size and complexity. In view of the bone abnormalities in CMS19, we here studied the tubular and calvarial bone morphology of the Col13a1−/− mice. We discovered several craniofacial malformations, albeit less pronounced ones than in the human disease, and a reduction of cortical bone mass in aged mice. In the Col13a1tm/tm mice, where ColXIII is synthesized but the ectodomain shedding is prevented due to a mutation in a protease recognition sequence, the cortical bone mass decreased as well with age and the cephalometric analyses revealed significant craniofacial abnormalities but no clear phenotypical pattern. To conclude, our data indicates an intrinsic role for ColXIII, particularly the soluble form, in the upkeep of bone with aging and suggests the possibility of previously undiscovered bone pathologies in patients with CMS19. [ABSTRACT FROM AUTHOR]

Sphingosine 1-phosphate (S1P) is a lipidic messenger known to exert several physiological functions within the cell. We tested here whether the stimulation of human monocytes with different doses of S1P might interfere with their differentiation into competent dendritic cells (DC). Monocytes cultured with granulocyte macrophage colony stimulating factor, interleukin-4 (IL-4) and S1P differentiated into a DC population lacking CD1a molecules on the surface and acquired some aspects of mature DC (mDC), though in the absence of maturation stimuli. When stimulated with lipopolisaccharide (LPS), CD1a− DC produce high amounts of tumour necrosis factor- α and IL-10, but not IL-12. Accordingly, these CD1a− DC were not capable of stimulating allogenic T lymphocytes so well as CD1a+ DC generated from untreated monocytes and maturated with LPS. S1P monocyte-derived DC lost their polarizing capacity abrogating the production of γ-interferon/IL-4 by co-cultured naïve CD4+CD45RA+ T cells. Our findings suggest a mechanism through which S1P can favour the development of immune-related pathological states. [ABSTRACT FROM AUTHOR]