SOCS-1 inhibits expression of the antiviral proteins 2′,5′-OAS and MxA induced by the novel interferon-λs IL-28A and IL-29

Brand, Stephan; Zitzmann, Kathrin; Dambacher, Julia; Beigel, Florian; Olszak, Torsten; Vlotides, George; Eichhorst, Sören T.; Göke, Burkhard; Diepolder, Helmut M.; Auernhammer, Christoph J.

doi:10.1016/j.bbrc.2005.04.004

Cited by 81 publications

(69 citation statements)

References 20 publications

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“…40,41 Furthermore, interferon response genes such as MxA and 5 0 3 0 OAS are activated 2 and subjected to typical regulatory mechanisms. 11 Although the IFN-l receptor is widely expressed, 2,3 expression of the ligand is tightly controlled and takes place after viral infection 2,17 or stimulation via many of the Toll-like receptors (TLRs), 15 a process that is elevated by IFN-a. 42 Expression via stimulation of TLR 7, 8 and 9 IFN-k1 downregulates the human Th2 response WJ Jordan et al is absolutely dependent on IRAK-4 signaling, whereas IFN-l1 can be transcribed following stimulation of the cell via TLR 3 or 4 in an IRAK-4-independent manner.…”

Section: Discussionmentioning

confidence: 99%

“…2 These observations, in conjunction with the induction of the IFN-l1/2/3 ligands by a range of viral infections and their ability to rescue virally infected cells, 2,3 have prompted a series of studies that have further investigated the antiviral properties of these cytokines. [8][9][10][11][12][13][14][15][16][17][18][19][20][21] However, the IFN-l ligands also induce the phosphorylation of STAT1, STAT3, STAT5 2,22 and STAT4. 23 Phosphorylation of STAT1, STAT3, STAT5 in particular, suggests more complex properties for the IFN-l ligand family; STAT3 is the signaling mechanism used by members of the IL-10 family (IL-10, IL-19, IL-20, etc.…”

Section: Introductionmentioning

confidence: 99%

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Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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Interferon lambda-1 (IFN-l1/IL-29) is a member of the Type-III interferon family, which contains three ligands: IFN-l1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-l-R1/IL-28Ra) and CRF2-4 (IL10-R-b) chains. Like their close relatives, the Type-I interferons, IFN-l1, 2 and 3, promote the phosphorylation of STAT1 and STAT2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit antiviral activity in vitro. Their use of the IL10-R-b chain and their ability to phosphorylate STAT3, STAT4 and STAT5 suggested that they may also exhibit immunomodulatory activity; their antiviral action led us to hypothesize that this activity might be directed toward the Th1/Th2 system. Here, we have demonstrated that IFN-l1 altered the activity of Th cells in three separate experimental systems: (i) mitogen stimulation, (ii) mixed-lymphocyte reaction (MLR) and (iii) stimulation of naive T cells by monocyte-derived dendritic cells (mDC). In Con-A stimulation assays, the inclusion of IFN-l1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-g. IL-13 secretion was 100-fold more sensitive to IFN-l1 than was IFN-g secretion. These observations were also made in the allogeneic two-way MLR. IFN-l1 was able to alter cytokine-mediated Th biasing and when naive T cells were exposed to allogeneic mDC that had been matured in the presence of IFN-l1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-g was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-l1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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“…28 Combination treatment with IFN-a and IL-29/28A enhanced the antiviral effect against HCV replicon synergistically. 29 As described above, HCV replication is inhibited by the antiviral effects of IFN-l. A pegylated IFN-l1 has already been tried against chronic hepatitis C in phase 2 trials. 30,31 Interestingly, impressive antiviral effects (at least as good as with PegIFN-a) were observed but with fewer and less severe side effects.…”

Section: Il-28b and Its Function Against Hcvmentioning

confidence: 92%

Discovery of critical host factor, IL‐28B, associated with response to hepatitis C virus treatment

Mizokami

2012

J of Gastro and Hepatol

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Chronic hepatitis C affects 2.2-3.0% of the world population (130 million-170 million). Pegylated interferon-a (PEG-IFN-a) in combination with ribavirin (RBV), the approved and standard therapy, leads to viral eradication in about 50% of treated patients. In 2009, genome-wide association studies (GWAS) identified host genetic variation to be critical for predicting treatment response and spontaneous clearance in patients infected with hepatitis C virus (HCV). A correlated set of polymorphisms in the region of the interleukin-28B (IL-28B) gene on chromosome 19, coding for interferon (IFN)-l3 were associated with clearance of genotype 1 hepatitis C virus (HCV) in patients treated with PEG-IFN-a and RBV. The same polymorphisms were subsequently associated with spontaneous clearance of HCV in untreated patients. In addition, prediction of viral response to PEG-IFN-a and RBV therapy of patients with recurrent HCV infection after orthotopic liver transplantation depends on the IL-28B genotype of both recipient and donor tissues. Diagnosis of a patient's IL-28B genotype is likely to aid in clinical decision making with standard-of-care regimens. Future studies will investigate the possibility of individualizing treatment duration and novel regimens according to IL-28B genotype. As GWAS yield unexpected data, this approach could lead to the development of novel drug therapy, such as already appears promising with IFN-l. In this Okuda lecture, I present the current understanding in regard to the relationship between host variations and clinical outcome of hepatitis C.

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“…Type III IFNs induce the formation of both ISGF3 and STAT1 homodimers, which are able to recognize ISRE and GAS sequences [12,14,23]. Among the IFN-induced genes, suppressor of cytokine signaling (SOCS)1 and SOCS3 are involved in the negative regulation of type III IFN signaling [51,52]. Overexpression of SOCS1 in hepatic cell lines inhibits type III IFN signaling as well [51].…”

Section: Signal Transduction Of Type III Ifnsmentioning

confidence: 99%