ABSTRACT
The generation of diversity and plasticity of transcriptional programs are key components of effective vertebrate immune responses. The role of Alternative Splicing has been recognized, but it is underappreciated and poorly understood as a critical mechanism for the regulation and fine-tuning of physiological immune responses. Here we report the generation of loss-of-function phenotypes for a large collection of genes known or predicted to be involved in the splicing reaction and the identification of 19 novel regulators of IL-1ß secretion in response to E. coli challenge of THP-1 cells. Twelve of these genes are required for IL-1ß secretion, while seven are negative regulators of this process. Silencing of SFRS3 increased IL-1ß secretion due to elevation of IL-1ß and caspase-1 mRNA in addition to active caspase-1 levels. This study points to the relevance of splicing in the regulation of auto-inflammatory diseases.
Subject(s)
Interleukin-1beta/metabolism , RNA Splicing/genetics , RNA, Small Interfering/metabolism , RNA-Binding Proteins/metabolism , Caspase 1/metabolism , Cell Line , Enzyme Activation , Escherichia coli , Gene Expression Regulation , Gene Silencing , Genes, Reporter , Humans , Interleukin-1beta/genetics , Monocytes/metabolism , NF-kappa B/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , Reproducibility of Results , Serine-Arginine Splicing Factors , Transcription, GeneticABSTRACT
An easy route to cationic beta-vinyl substituted meso-tetraphenylporphyrin derivatives is described. Two novel compounds were tested in vitro for their antiviral photoactivity against herpes simplex virus type 1. One of these compounds exhibited a significant activity, reaching 99% of virus inactivation after 15 min of photoactivation.
