Organ-Specific Expression of IL-1 Receptor Results in Severe Liver Injury in Type I Interferon Receptor Deficient Mice

Abstract

Upon treatment with polyinosinic:polycytidylic acid [poly(I:C)], an artificial double-stranded RNA, type I interferon receptor-deficient (IFNAR −/− ) mice develop severe liver injury seen by enhanced alanine aminotransferase (ALT) activity in the serum that is not observed in their wildtype (WT) counterparts. Recently, we showed that liver injury is mediated by an imbalanced expression of interleukin (IL)-1β and its receptor antagonist (IL1-RA) in the absence of type I IFN. Here we show that despite comparable expression levels of IL-1β in livers and spleens, spleens of poly(I:C)-treated IFNAR −/− mice show no signs of injury. In vitro analyses of hepatocytes and splenocytes revealed that poly(I:C) had no direct toxic effect on hepatocytes. Furthermore, expression levels of cytokines involved in other models for liver damage or protection such as interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-6, IL-10, IL-17, and IL-22 were comparable for both organs in WT and IFNAR −/− mice upon treatment. Moreover, flow cytometric analyses showed that the composition of different immune cells in livers and spleens were not altered upon injection of poly(I:C). Finally, we demonstrated that the receptor binding IL-1β, IL1R1, is specifically expressed in livers but not spleens of WT and IFNAR −/− mice. Accordingly, mice double-deficient for IFNAR and IL1R1 developed no liver injury upon poly(I:C) treatment and showed ALT activities comparable to those of WT mice. Collectively, liver injury is mediated by the organ-specific expression of IL1R1 in the liver.

The Bio-Persistence of Reversible Inflammatory, Histological Changes and Metabolic Profile Alterations in Rat Livers after Silver/Gold Nanorod Administration

“…Although the expression levels of all the tested cytokines were elevated by Au@Ag NRs at 2 w, among all the tested pro-inflammatory Th1 type cytokines, only IL-1β and IL-2 still remained relatively higher levels at 8 w. As previously reported, AgNPs induced inflammasome and significantly high levels of IL-1β production in Hep G2 cells, a human hepatoma cell line [50]. Recently, it has been confirmed that an imbalanced expression of IL-1β could mediate liver injury [51]. AgNPs can also lead to the significant increase of IL-1β in primary rat brain microvessel endothelial cells (rBMEC) [52].…”

Interleukin-36γ is causative for liver damage upon infection with Rift Valley fever virus in type I interferon receptor-deficient mice

“…Thus, we isolated livers of IFNAR -/and WT mice 30 hours post RVFV cl13 infection and analyzed IL-1b (Figure 2A) and IL-1RA (Figure 2B) induction by ELISA. Unlike poly(I:C)-treated animals (11,12), RVFV cl13-infected IFNAR -/mice showed high IL-1b as well as IL-1RA expression while WT mice did not show any IL-1b or IL-1RA induction upon infection.…”

“…Next, we aimed to investigate if liver damage upon RVFV cl13 infection is mediated by a dysregulation of the IL-1 family members IL-1b and/or IL-1RA as it has been shown before for poly(I:C) treatment (11,12). Thus, we isolated livers of IFNAR -/and WT mice 30 hours post RVFV cl13 infection and analyzed IL-1b (Figure 2A) and IL-1RA (Figure 2B) induction by ELISA.…”

“…Deficient type I IFN signaling was associated with increased levels of IL-1b, which in turn was causative for the induction of severe liver damage as shown e.g. by high activity of serum alanine aminotransferase (ALT) (11,12). As many viruses produce double-stranded RNA during their life cycle, poly(I:C) resembles a good model for a viral infection.…”

RNA-Sequencing Characterization of lncRNA and mRNA Functions in Septic Pig Liver Injury

“…The interleukin-1 receptor type 1 (IL1R1) gene was predicted as a DETG of LNC_003307 and was significantly increased in pig liver after the LPS challenge. Anzaghe et al [ 47 ] have previously demonstrated that the organ-specific expression of IL1R1 treatment mediates poly(I:C)-induced IL-1β-mediated liver injury. In addition, the JAK2-STAT1/STAT3 signaling pathway plays an important role in initiating inflammatory response following LPS [ 48 , 49 ].…”