Retinoic acid-inducible gene-I (RIG-I) is induced by IFN-γ in human mesangial cells in culture: possible involvement of RIG-I in the inflammation in lupus nephritis

Abstract

Interferon-gamma is a potent Th1-type cytokine and a key molecule in the pathogenesis of autoimmune diseases including lupus nephritis. Retinoic acid-inducible gene-I is a putative RNA helicase that plays an important role in immune and inflammatory reactions. We previously demonstrated the increased expression of the retinoic acid-inducible gene-I protein in the kidney tissue of patients with lupus nephritis, and the presence of a significant amount of retinoic acid-inducible gene-I mRNA in the urinary sediment of patients with this inflammatory renal disease. In the present study, interferon-gamma was found to induce the expression of retinoic acid-inducible gene-I in human mesangial cells in culture. Knockdown of retinoic acid-inducible gene-I inhibited the interferon-gamma-induced upregulation of interferon regulatory factor 7, a transcriptional factor involved in immune and inflammatory reactions. These findings suggest that retinoic acid-inducible gene-I produced by mesangial cells may be involved in the pathogenesis of lupus nephritis.

RA-inducible gene-I induction augments STAT1 activation to inhibit leukemia cell proliferation

“…As mentioned above (28,29), Rig-I itself was an authentic ISG, and its mRNA level in normal myeloid cells was significantly elevated by either IFN-α or IFN-γ stimulation ( Fig. 2 B and C).…”

“…Nevertheless, because RIG-I expression itself is highly inducible by IFN or RA signaling (Fig. S2 B and C) (21,28,29), we argue that RIG-I might also possess a relatively independent regulatory role on the ensuing IFN intracellular signaling process. In line with this assumption, we have previously demonstrated an important physiological role of RIG-I in negatively regulating myelopoiesis, partly through maintaining the myeloid expression of a classic ISG, Icsbp (19).…”

“…Actually, previous studies have already shown that in the absence of viral infection, RIG-I overexpression alone in the mammalian cell line BEAS-2B results in the induction of STAT1 mRNA (28) and that IFN-γ-stimulated expression of IFN regulatory factor 7 is dependent on RIG-I (29). In this present study with the Tc − -inducible expression of RIG-I in the U937 cell line, the dual effects of RIG-I not only on elevating the STAT1 mRNA level but also on enhancing STAT1 phosphorylation, at least at the 701 site, were clearly demonstrated.…”

Treatment of Pediatric-Onset Lupus Nephritis: A New Option of Less Cytotoxic Immunosuppressive Therapy

“…In contrast, IFN-did not induce the expression of IFN-, which is known to be a target gene of IRF-7, in mesangial cells (Fig. 3) (Imaizumi et al, 2010) Interestingly, pretreatment of cells with dexamethasone inhibited the IFN--induced expression of monocyte chemoattractant protein (MCP)-1 mRNA but did not affect the induction of RIG-I or IRF7 mRNA in mesangial cells. The induction of MCP-1 mRNA by IFN-was not inhibited by the knockdown of NF-κB p65, indicating that the NF-κB signaling pathway was not involved.…”

“…3. (Imaizumi et al, Lupus 2010) In a recent study, we showed that RIG-I controlled the immune and inflammatory responses by regulating the expression of various downstream genes, including IFNs regulatory factor (IRF) genes, in mesangial cells (Imaizumi et al, 2010). We previously found RIG-I was highly expressed in the glomeruli examined in biopsy specimens from patients with lupus nephritis, and the level of expression correlated with the severity of acute inflammatory lesions (Suzuki et al, 2007).…”