miR-223: infection, inflammation and cancer.

Expression of the microRNA miR-223 is deregulated during influenza or hepatitis B infection and in inflammatory bowel disease, type 2 diabetes, leukaemia and lymphoma. Although this may also be the result of the disease per se, increasing evidence suggests a role for miR-223 in limiting inflammation to prevent collateral damage during infection and in preventing oncogenic myeloid transformation. Validated targets for miR-223 that have effects on inflammation and infection include granzyme B, IKKα, Roquin and STAT3. With regard to cancer, validated targets include C/EBPß, E2F1, FOXO1 and NFI-A. The effect of miR-223 on these targets has been documented individually; however, it is more likely that miR-223 affects multiple targets simultaneously for key processes where the microRNA is important. Such processes include haematopoietic cell differentiation, particularly towards the granulocyte lineage (where miR-223 is abundant) and as cells progress down the myeloid lineage (where miR-223 expression decreases). NF-κB and the NLRP3 inflammasome are important inflammatory mechanisms that are dampened by miR-223 in these cell types. The miRNA can also directly target viruses such as HIV, leading to synergistic effects during infection. Here we review the recent studies of miR-223 function to show how it modulates inflammation, infection and cancer development.

Mycoplasma fermentans inhibits tumor necrosis factor alpha-induced apoptosis in the human myelomonocytic U937 cell line.

Mycoplasma fermentans (M. fermentans) was shown to be involved in the alteration of several eukaryotic cell functions (i.e. cytokine production, gene expression), and was suggested as a causative agent in arthritic diseases involving impaired apoptosis. We investigated whether M. fermentans has a pathogenic potential by affecting tumor necrosis factor (TNF)alpha-induced apoptosis in the human myelomonocytic U937 cell line. A significant reduction in the TNFalpha-induced apoptosis (approximately 60%) was demonstrated upon either infection with live M. fermentans or by stimulation with non-live M. fermentans. To investigate the mechanism of M. fermentans antiapoptotic effect, the reduction of mitochondrial transmembrane potential (DeltaPsim) and the protease activity of caspase-8 were measured. In the infected cells, the reduction of DeltaPsim was inhibited (approximately 75%), and an approximately 60% reduction of caspase-8 activity was measured. In conclusion, M. fermentans significantly inhibits TNFalpha-induced apoptosis in U937 cells, and its effect is upstream of the mitochondria and upstream of caspase-8.