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Interleukin-19 impairment in active Crohn s disease patients Canto E; Garcia Planella E; Zamora-Atenza C; Nieto JC; Gordillo J; Ortiz MA; Meton I; Serrano E; Vegas E; Garcia-Bosch O; Juarez C; Vidal SPLoS One 2014[]; 9 (4): e93910The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNFalpha and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investigate the expression and effects of IL-19 on cells from active Crohn's disease (CD) patient. Twenty-three active CD patients and 20 healthy controls (HC) were included. mRNA and protein IL-19 levels were analyzed in monocytes. IL-19 effects were determined in vitro on the T cell phenotype and in the production of cytokines by immune cells. We observed that unstimulated and TLR-activated monocytes expressed significantly lower IL-19 mRNA in active CD patients than in HC (logFC = -1.97 unstimulated; -1.88 with Pam3CSK4; and -1.91 with FSL-1; p<0.001). These results were confirmed at protein level. Exogenous IL-19 had an anti-inflammatory effect on HC but not on CD patients. IL-19 decreased TNFalpha production in PBMC (850.7 +/- 75.29 pg/ml vs 2626.0 +/- 350 pg/ml; p<0.01) and increased CTLA4 expression (22.04 +/- 1.55% vs 13.98 +/- 2.05%; p<0.05) and IL-4 production (32.5 +/- 8.9 pg/ml vs 13.5 +/- 2.9 pg/ml; p<0.05) in T cells from HC. IL-10 regulated IL-19 production in both active CD patients and HC. We observed that three of the miRNAs that can modulate IL-19 mRNA expression, were up-regulated in monocytes from active CD patients. These results suggested that IL-19 had an anti-inflammatory role in this study. Defects in IL-19 expression and the lack of response to this cytokine could contribute to inflammatory mechanisms in active CD patients.|Adult[MESH]|Aged[MESH]|CTLA-4 Antigen/biosynthesis/genetics[MESH]|Cells, Cultured[MESH]|Crohn Disease/immunology/*metabolism[MESH]|Female[MESH]|Gene Expression Profiling[MESH]|Gene Expression Regulation[MESH]|Humans[MESH]|Interleukin-10/physiology[MESH]|Interleukins/biosynthesis/blood/*deficiency/genetics/pharmacology[MESH]|Leukocytes, Mononuclear/metabolism[MESH]|Lymphocyte Activation/drug effects[MESH]|Male[MESH]|MicroRNAs/genetics[MESH]|Middle Aged[MESH]|Monocytes/*metabolism[MESH]|Recombinant Proteins/pharmacology[MESH]|Th2 Cells/immunology[MESH]|Toll-Like Receptors/genetics/physiology[MESH]|Tumor Necrosis Factor-alpha/metabolism[MESH] |
