Interferon-Stimulated Gene 15, a Type I Interferon-Dependent Transcript, Is Involved in a Negative Feedback Loop in Innate Immune Reactions in Human Mesangial Cells

摘要

Background: Since innate immunity plays a pivotal role in the pathogenesis of glomerulonephritis, the activation of toll-like receptor (TLR) 3/type I interferon (IFN) cascades is important in glomerular inflammation. However, the role of IFN-stimulated gene 15 (ISG15), a type IFN-dependent transcript, in glomerular inflammation is unclear. We, therefore, examined the role of ISG15 in innate immune reactions induced by TLR3 signaling in cultured human mesangial cells (MCs). Methods: We treated MCs with polyinosinic-polycyt-idylic acid (poly IC), an authentic double-stranded RNA, and analyzed the ISG15 expression by reverse transcription-poly-merase chain reaction and western blotting. To examine the regulation of ISG15 expression, we subjected MCs to RNA interference (siRNA) against TLR3, IFN-3, ISG56, and melanoma differentiation-associated gene 5 (MDA5).