RelAp43, a Member of the NF-κB Family Involved in Innate Immune Response against Lyssavirus Infection

Luco, Sophie; Delmas, Olivier; Vidalain, Pierre‐Olivier; Tangy, Frédéric; Weil, Robert; Bourhy, Hervé

doi:10.1371/journal.ppat.1003060

Cited by 37 publications

(59 citation statements)

References 64 publications

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“…We then examined the involvement of NF-κB, a transcription factor that plays a crucial role in inflammation, immunity, cell proliferation and apoptosis (25)(26)(27)(28). NF-κB affected the LPS-induced E-selectin and ICAM-1 expression.…”

Section: Inhibition Of Mapk and Nf-κb Pathways Suppresses The Mrna Exmentioning

confidence: 99%

Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling

Liu

Wei

et al. 2013

International Journal of Molecular Medicine

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Abstract. The expression of adhesion molecules in endothelial cells elicited by lipopolysaccharide (LPS) is involved in the adhesive interaction between endothelial cells and monocytes in inflammation. In this study, in order to characterize the anti-inflammatory effects of chitosan oligosaccharides (COS) on LPS-induced inflammation and to elucidate the underlying mechanisms, the mRNA levels of E-selectin and intercellular adhesion molecule-1 (ICAM-1) were measured in porcine iliac artery endothelial cells (PIECs). When these cells were treated with COS, the LPS-induced mRNA expression of E-selectin and ICAM-1 was reduced through the inhibition of the signal transduction cascade, p38 mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB). Moreover, through the inhibition of p38 MAPK and ERK1/2, COS suppressed the LPS-induced NF-κB p65 translocation. We found that COS suppressed the phosphorylation of p38 MAPK and the translocation of NF-κB p65 into the nucleus in a dose-dependent manner, and inhibited the adhesion of U973 cells to PIECs. Based on these results, it can be concluded that COS downregulate the expression of E-selectin and ICAM-1 by inhibiting the phosphorylation of MAPKs and the activation of NF-κB in LPS-treated PIECs. Our study demonstrates the valuable anti-inflammatory properties of COS. IntroductionChitosan oligosaccharides (COS), consisting of D-glucosamine linked via β-1,4-glycosides, are derived from chitosan by chemical or enzymatic hydrolysis (1). It has been reported that COS exhibit various biological activities, such as antitumor (2) and antioxidant properties (3), owing to their low molecular weight, high absorption, solubility and biocompatibility (4). In addition, recent studies have paid more attention to the regulatory role of COS in inflammatory responses (5,6).Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, can act as an endotoxin and initiates serious inflammatory responses in vitro and in vivo (7,8) by upregulating the expression of adhesion molecules and cytokines, such as E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and tumor necrosis factor-α (TNF-α) (9,10). Endothelial cells are the target of inflammatory responses and thereby, of a number of severe disorders, including sepsis and multiple organ dysfunctions that occur via LPS stimulation (11). In this study, we detected the expression of the adhesion molecules, E-selectin and ICAM-1 in LPS-treated porcine iliac artery endothelial cells (PIECs), since the upregulation of adhesion molecules and the increased secretion of cytokines and chemokines are known to occur during endothelial cell activation (12)(13)(14).The evolutionary conserved family of mitogen-activated protein kinases (MAPKs) includes extracellular p38 MAPK, extracellular regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) (15). Numerous environmental stresses, such as osmotic shock, ...

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Section: Inhibition Of Mapk and Nf-κb Pathways Suppresses The Mrna Exmentioning

confidence: 99%

Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling

Liu

Wei

et al. 2013

International Journal of Molecular Medicine

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“…Until recently, the NF-κB pathway was described as a family of five proteins in mammalian cells: p65/RelA, p50 (NF-κB 1), p52 (NF-κB 2), c-Rel and RelB. This list was recently enlarged with the characterization of a splicing variant of p65/RelA, called RelAp431. All NF-κB proteins share a structurally conserved N-terminal region, the Rel Homology Domain (RHD), which is critical for homo- or hetero-dimerization, nuclear localization, binding to DNA on κB sites and interaction with inhibitory proteins IκB.…”

mentioning

confidence: 99%

“…p50 and p52 form transcriptionally active heterodimers with either p65/RelA, c-Rel or RelB23. RelAp43 can also form heterodimers with the five other members of the NF-κB family, including p65/RelA and p50, and activate transcription of NF-κB dependent genes1. Rel proteins (p65/RelA, c-Rel and RelB) contain a C-terminal transactivation domain (TAD), which is lacking in RelAp43, p50 and p521.…”

mentioning

confidence: 99%

“…RelAp43 can also form heterodimers with the five other members of the NF-κB family, including p65/RelA and p50, and activate transcription of NF-κB dependent genes1. Rel proteins (p65/RelA, c-Rel and RelB) contain a C-terminal transactivation domain (TAD), which is lacking in RelAp43, p50 and p521. Therefore, p50 and p52 form homodimers with no intrinsic ability to activate transcription and transcriptionally active heterodimers in association with p65, cRel, and RelB4.…”

mentioning

confidence: 99%

“…Beside its structural role in the virion of lyssavirus, the M protein is a potent modulator of apoptosis after lyssavirus infection262728. It is also able to target RelAp43, thus inducing an inhibition of NF-κB signaling and a reduction in IFN-β transcription1. Furthermore, this modulation is highly dependent on the strain of lyssavirus considered.…”

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confidence: 99%

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The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity

Khalifa

Luco

Besson

et al. 2016

Sci Rep

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The matrix (M) protein of wild isolates of rabies virus such as Tha (M-Tha) was previously shown to be able to interact with RelAp43, a protein of the NF-κB family, and to efficiently suppress NF-κB-dependent reporter gene expression, in contrast with the vaccine strain SAD. Here, we analyze the mechanisms involved in RelAp43-M protein interaction. We demonstrate that the central part of M-Tha, and the specific C-terminal region of RelAp43 are required for this interaction. Four differences in the corresponding amino acid sequences of the M-Tha and M-SAD are shown to be crucial for RelAp43 interaction and subsequent modulation of innate immune response. Furthermore, the capacity of M-Tha to interact with RelAp43 was shown to be crucial for the control of the expression of four genes (IFN, TNF, IL8 and CXCL2) during viral infection. These findings reveal that RelAp43 is a potent regulator of transcription of genes involved in innate immune response during rabies virus infection and that the M protein of wild isolates of rabies virus is a viral immune-modulatory factor playing an important role in this RelAp43-mediated host innate immunity response in contrast to M protein of vaccine strains, which have lost this property.

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Manipulation of Non-canonical NF-κB Signaling by Non-oncogenic Viruses

Struzik

Szulc-Dąbrowska

2018

Arch. Immunol. Ther. Exp.

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Nuclear factor (NF)-κB is a major regulator of antiviral response. Viral pathogens exploit NF-κB activation pathways to avoid cellular mechanisms that eliminate the infection. Canonical (classical) NF-κB signaling, which regulates innate immune response, cell survival and inflammation, is often manipulated by viral pathogens that can counteract antiviral response. Oncogenic viruses can modulate not only canonical, but also non-canonical (alternative) NF-κB activation pathways. The non-canonical NF-κB signaling is responsible for adaptive immunity and plays a role in lymphoid organogenesis, B cell development, as well as bone metabolism. Thus, non-canonical NF-κB activation has been linked to lymphoid malignancies. However, some data strongly suggest that the non-canonical NF-κB activation pathway may also function in innate immunity and is modulated by certain non-oncogenic viruses. Collectively, these findings show the importance of studying the impact of different groups of viral pathogens on alternative NF-κB activation. This mini-review focuses on the influence of non-oncogenic viruses on the components of non-canonical NF-κB signaling.

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RelAp43, a Member of the NF-κB Family Involved in Innate Immune Response against Lyssavirus Infection

Cited by 37 publications

References 64 publications

Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling

Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling

The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity

Manipulation of Non-canonical NF-κB Signaling by Non-oncogenic Viruses

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