Phylogenetic and genomic analyses of the ribosomal oxygenases Riox1 (No66) and Riox2 (Mina53) provide new insights into their evolution

in BMC Ecology and Evolution (2018), 18(96),

Translation of specific mRNAs can be highly regulated in different cells, tissues or under pathological conditions. Ribosome heterogeneity can originate from variable expression or post-translational ... [more ▼]

Translation of specific mRNAs can be highly regulated in different cells, tissues or under pathological conditions. Ribosome heterogeneity can originate from variable expression or post-translational modifications of ribosomal proteins. The ribosomal oxygenases RIOX1 (NO66) and RIOX2 (MINA53) modify ribosomal proteins by histidine hydroxylation. A similar mechanism is present in prokaryotes. Thus, ribosome hydroxylation may be a well-conserved regulatory mechanism with implications in disease and development. However, little is known about the evolutionary history of Riox1 and Riox2 genes and their encoded proteins across eukaryotic taxa. [less ▲]

1alpha,25-Dihydroxyvitamin D3 is a potent suppressor of interferon gamma-mediated macrophage activation.

in Blood (2005), 106(13), 4351-8

1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3), the activated vitamin D3 hormone, is a key regulator of calcium homeostasis and thereby indispensable for bone metabolism. In addition, 1alpha,25(OH)2D3 ... [more ▼]

1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3), the activated vitamin D3 hormone, is a key regulator of calcium homeostasis and thereby indispensable for bone metabolism. In addition, 1alpha,25(OH)2D3 is known to mediate predominantly immunosuppressive responses in vitro and in vivo. It has been demonstrated that macrophages can produce 1alpha,25(OH)2D3 on activation with interferon gamma (IFN-gamma), although little is understood about the biologic significance of this response. We show here that 1alpha,25(OH)2D3 can selectively suppress key effector functions of IFN-gamma-activated macrophages. Among these are the suppression of listericidal activity, the inhibition of phagocyte oxidase-mediated oxidative burst, and the suppression of important IFN-gamma-induced genes, including Ccl5, Cxcl10, Cxcl9, Irf2, Fcgr1, Fcgr3, and Tlr2. The deactivation of IFN-gamma-stimulated macrophages is dependent on a functional vitamin D receptor and 1alpha,25(OH)2D3 acts specifically on IFN-gamma-activated macrophages, whereas the steroid has no effects on resting macrophages. Therefore, the 1alpha,25(OH)2D3-mediated suppression of macrophage functions is distinct from previously described macrophage deactivation mechanisms. In conclusion, our data indicate that the production of 1alpha,25(OH)2D3 by IFN-gamma-stimulated macrophages might be an important negative feedback mechanism to control innate and inflammatory responses of activated macrophages. [less ▲]