scholarly journals Interleukin-1? repressesMRP2 gene expression through inactivation of interferon regulatory factor 3 in HepG2 cells

Hepatology ◽  
2004 ◽  
Vol 39 (6) ◽  
pp. 1574-1582 ◽  
Author(s):  
Keiji Hisaeda ◽  
Akihiko Inokuchi ◽  
Takanori Nakamura ◽  
Yukihide Iwamoto ◽  
Kimitoshi Kohno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepg2 Cells ◽  
Interleukin 1 ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3

scholarly journals Regulation of Type I Interferon Gene Expression by Interferon Regulatory Factor-3

1998 ◽  
Vol 273 (5) ◽  
pp. 2714-2720 ◽  
Author(s):  
Susan L. Schafer ◽  
Rongtuan Lin ◽  
Paul A. Moore ◽  
John Hiscott ◽  
Paula M. Pitha
Keyword(s):  
Gene Expression ◽  
Type I Interferon ◽  
Interferon Regulatory Factor ◽  
Type I ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Interferon Gene

scholarly journals Distinct Functions of the Mitogen-activated Protein Kinase-activated Protein (MAPKAP) Kinases MK2 and MK3

2011 ◽  
Vol 286 (27) ◽  
pp. 24113-24124 ◽  
Author(s):  
Christian Ehlting ◽  
Natalia Ronkina ◽  
Oliver Böhmer ◽  
Ute Albrecht ◽  
Konrad A. Bode ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Nuclear Translocation ◽  
Interferon Regulatory Factor ◽  
Mitogen Activated Protein Kinase ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Downstream Signaling ◽  
Enhanced Expression ◽  
Regulatory Effects

In LPS-treated macrophages, activation of STAT3 is considered to be crucial for terminating the production of inflammatory cytokines. By analyzing the role of MAPK-activated protein kinase (MK) 2 and MK3 for LPS-induced STAT3 activation in macrophages, the present study provides evidence that MK2 is crucial for STAT3 activation in response to LPS because it prevents MK3 from impeding IFNβ gene expression. Accordingly, LPS-induced IFNβ gene expression is down-regulated in MK2-deficient macrophages and can be reconstituted by additional ablation of the MK3 gene in MK2/3−/− macrophages. This is in contrast to LPS-induced IL-10 expression, which essentially requires the presence of MK2. Further analysis of downstream signaling events involved in the transcriptional regulation of IFNβ gene expression suggests that, in the absence of MK2, MK3 impairs interferon regulatory factor 3 protein expression and activation and inhibits nuclear translocation of p65. This inhibition of p65 nuclear translocation coincides with enhanced expression and delayed degradation of IκBβ, whereas expression of IκBα mRNA and protein is impaired in the absence of MK2. The observation that siRNA directed against IκBβ is able to reconstitute IκBα expression in MK2−/− macrophages suggests that enhanced expression and delayed degradation of IκBβ and impaired NFκB-dependent IκBα expression are functionally linked. In summary, evidence is provided that MK2 regulates LPS-induced IFNβ expression and downstream STAT3 activation as it restrains MK3 from mediating negative regulatory effects on NFκB- and interferon regulatory factor 3-dependent LPS signaling.

scholarly journals Rhesus Cytomegalovirus Particles Prevent Activation of Interferon Regulatory Factor 3

2005 ◽  
Vol 79 (10) ◽  
pp. 6419-6431 ◽  
Author(s):  
Victor DeFilippis ◽  
Klaus Früh
Keyword(s):  
Gene Expression ◽  
Viral Gene Expression ◽  
Interferon Regulatory Factor ◽  
Nuclear Accumulation ◽  
Pcr Analysis ◽  
Viral Gene ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Infected Cells ◽  
Irf3 Activation

ABSTRACT One of the most important innate host defense mechanisms against viral infection is the induction of interferon (IFN)-stimulated genes (ISGs). Immediately upon entry, viruses activate interferon-regulatory factor 3 (IRF3), as well as nuclear factor κB (NF-κB), which transactivate a subset of ISGs, proinflammatory genes, as well as IFN genes. Most large DNA viruses exhibit countermeasures against induction of this response. However, whereas human cytomegalovirus (HCMV) inhibits IFN-dependent induction of ISGs, IFN-independent induction of ISGs is observed both in the presence and, even moreso, in the absence of viral gene expression. Rhesus CMV (RhCMV) is an emerging animal model for HCMV sharing important similarities in primary structure, epidemiology, and pathogenesis. To determine whether RhCMV would similarly induce ISGs, we performed DNA microarray and quantitative PCR analysis of ISG expression in rhesus fibroblasts infected with RhCMV or HCMV. In contrast to HCMV, however, RhCMV did not induce expression of ISGs or proinflammatory genes at any time after infection. Moreover, dimerization and nuclear accumulation of IRF3, readily observed in HCMV-infected cells, was absent from RhCMV-infected cells, whereas neither virus seemed to activate NFκB. RhCMV also blocked IRF3 activation by live or UV-inactivated HCMV, suggesting that RhCMV inhibits viral IRF3 activation and the resultant ISG induction with extraordinary efficiency. Since infection during inhibition of protein expression by cycloheximide or inactivation of viral gene expression by UV treatment did not trigger IRF3 activation or ISG expression by RhCMV, we conclude that RhCMV virions contain a novel inhibitor of IFN-independent viral induction of ISG expression by IRF3.

scholarly journals Interferon regulatory factor 3 inhibits astrocyte inflammatory gene expression through suppression of the proinflammatory miR-155 and miR-155*

Glia ◽  
2011 ◽  
Vol 59 (12) ◽  
pp. 1911-1922 ◽  
Author(s):  
Leonid Tarassishin ◽  
Olivier Loudig ◽  
Avital Bauman ◽  
Bridget Shafit-Zagardo ◽  
Hyeon-Sook Suh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

scholarly journals Deregulation of HDAC5 by Viral Interferon Regulatory Factor 3 Plays an Essential Role in Kaposi's Sarcoma-Associated Herpesvirus-Induced Lymphangiogenesis

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Hye-Ra Lee ◽  
Fan Li ◽  
Un Yung Choi ◽  
Hye Ryun Yu ◽  
Grace M. Aldrovandi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Global Gene Expression ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Kshv Infection ◽  
Specific Manner

ABSTRACTKaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi’s sarcoma (KS), which is one of the most common HIV-associated neoplasms. The endothelium is the thin layer of squamous cells where vascular blood endothelial cells (BECs) line the interior surface of blood vessels and lymphatic endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS lesions contain a prominent compartment of neoplastic spindle morphology cells that are closely related to LECs. Furthermore, while KSHV can infect both LECs and BECsin vitro, its infection activates genetic programming related to lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are involved in KSHV infection and malignancy. Here, we report for the first time that viral interferon regulatory factor 3 (vIRF3) is readily detected in over 40% of KS lesions and that vIRF3 functions as a proangiogenic factor, inducing hypersprouting formation and abnormal growth in a LEC-specific manner. Mass spectrometry analysis revealed that vIRF3 interacted with histone deacetylase 5 (HDAC5), which is a signal-responsive regulator for vascular homeostasis. This interaction blocked the phosphorylation-dependent cytosolic translocation of HDAC5 and ultimately altered global gene expression in LECs but not in BECs. Consequently, vIRF3 robustly induced spindle morphology and hypersprouting formation of LECs but not BECs. Finally, KSHV infection led to the hypersprouting formation of LECs, whereas infection with a ΔvIRF3 mutant did not do so. Collectively, our data indicate that vIRF3 alters global gene expression and induces a hypersprouting formation in an HDAC5-binding-dependent and LEC-specific manner, ultimately contributing to KSHV-associated pathogenesis.IMPORTANCESeveral lines of evidences indicate that KSHV infection of LECs induces pathological lymphangiogenesis and that the results resemble KS-like spindle morphology. However, the underlying molecular mechanism remains unclear. Here, we demonstrated that KSHV vIRF3 is readily detected in over 40% of various KS lesions and functions as a potent prolymphangiogenic factor by blocking the phosphorylation-dependent cytosolic translocation of HDAC5, which in turn modulates global gene expression in LECs. Consequently, vIRF3-HDAC5 interaction contributes to virus-induced lymphangiogenesis. The results of this study suggest that KSHV vIRF3 plays a crucial role in KSHV-induced malignancy.

Sign in / Sign up

Export Citation Format

Share Document