Dengue Virus Infection Induced NF-κB-dependent Macrophage Migration Inhibitory Factor Production

Chen, Lien Cheng; Shyu, Huey Wen; Lei, Huan Yao; Chen, Shun Hua; Liu, Hsiao Sheng; Lin, Yee Shin; Yeh, Trai Ming

doi:10.3844/ajidsp.2008.22.31

Cited by 6 publications

(3 citation statements)

References 18 publications

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“…MIF is a chemokine-like inflammatory cytokine that binds to cell surface receptors (CD74 and/or CXCR2/4/7) and activates downstream signals, such as MAPK/ERK, to modulate inflammatory and immune responses [ 20 – 25 ]. DENV infection can induce MIF secretion [ 26 , 27 ], and the concentration of MIF is positively correlated with dengue severity [ 28 ]. Furthermore, DENV infection-induced disease was found to be less severe in MIF knockout ( Mif -/- ) mice than in normal mice [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability

et al. 2018

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Vascular leakage is one of the salient characteristics of severe dengue. Nonstructural protein 1 (NS1) of dengue virus (DENV) can stimulate endothelial cells to secrete endothelial hyperpermeability factor, macrophage migration inhibitory factor (MIF), and the glycocalyx degradation factor heparanase 1 (HPA-1). However, it is unclear whether MIF is directly involved in NS1-induced glycocalyx degradation. In this study, we observed that among NS1, MIF and glycocalyx degradation-related molecules, the HPA-1, metalloproteinase 9 (MMP-9) and syndecan 1 (CD138) serum levels were all increased in dengue patients, and only NS1 and MIF showed a positive correlation with the CD138 level in severe patients. To further characterize and clarify the relationship between MIF and CD138, we used recombinant NS1 to stimulate human cells in vitro and challenge mice in vivo. Our tabulated results suggested that NS1 stimulation could induce human endothelial cells to secrete HPA-1 and immune cells to secrete MMP-9, resulting in endothelial glycocalyx degradation and hyperpermeability. Moreover, HPA-1, MMP-9, and CD138 secretion after NS1 stimulation was blocked by MIF inhibitors or antibodies both in vitro and in mice. Taken together, these results suggest that MIF directly engages in dengue NS1-induced glycocalyx degradation and that targeting MIF may represent a possible therapeutic approach for preventing dengue-induced vascular leakage.

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Section: Introductionmentioning

confidence: 99%

Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability

et al. 2018

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“…Moreover, minocycline is reported to reduce the production of TNF-α, IL-6, IL-12, IFN-γ and CCL2 via suppression of the transcription factor NF-κB in the brain, which confers complete protection against JEV in mice [102]. NF-κB binds to the MIF promoter and drives MIF transcription [103], and inhibition of NF-B also blocks DENV infection-induced MIF production in A549 cells [104]; therefore, attenuation of de novo RNA synthesis and secretion of MIF from DENV-infected cells by minocycline treatment may be due to its inhibition of the NF-κB signal pathway and suppression of the ABC transporter, respectively [105]. However, further study is required to clarify these hypotheses.…”

Section: Minocycline Attenuates Denv Replication By Targeting Mifmentioning

confidence: 99%

Roles of Macrophage Migration Inhibitory Factor in Dengue Pathogenesis: From Pathogenic Factor to Therapeutic Target

2020

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Dengue virus (DENV) infection is the most prevalent mosquito-borne viral infection and can lead to severe dengue hemorrhagic fever (DHF) and even life-threatening dengue shock syndrome (DSS). Although the cytokine storm has been revealed as a critical factor in dengue disease, the limited understanding of dengue immunopathogenesis hinders the development of effective treatments. Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine that mediates diverse immune responses, and the serum level of MIF positively correlates with disease severity in patients with dengue. MIF is involved in DENV replication and many pathological changes, such as vascular leakage, during DENV infection. In this paper, the pathogenic roles of MIF and the regulation of MIF secretion during DENV infection are reviewed. Furthermore, whether MIF is a potential therapeutic target against DENV infection is also discussed.

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“…DENV infection, but not stimulation with UV-inactivated DENV, induces MIF secretion in a dose- and time-dependent manner in the human epithelial cell line A549 [ 46 ]. A MIF promoter assay and reverse transcription polymerase chain reaction (RT-PCR) demonstrate that MIF gene transcription is activated during DENV infection.…”

Section: Mif Production Induced By Denv Infectionmentioning

confidence: 99%

Pathogenic Roles of Macrophage Migration Inhibitory Factor during Dengue Virus Infection

Chuang

Chen

Yeh

2015

Mediators of Inflammation

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Dengue virus (DENV) infection is the most common cause of viral hemorrhagic fever, which can lead to life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Hemorrhage and plasma leakage are two major hallmarks of DHF/DSS. Because the mechanisms causing these pathogenic changes are unclear, there is no effective therapy against DHF/DSS. In this review, we focus on the possible pathogenic effects of a pleiotropic cytokine, macrophage migration inhibitory factor (MIF), on the pathogenesis of DENV infection. MIF is a critical mediator of the host immune response and inflammation, and there is a correlation between the serum levels of MIF and disease severity in dengue patients. Furthermore, MIF knock-out mice exhibit less severe clinical disease and lethality. However, the role of MIF in the pathogenesis of DHF/DSS is not limited to immune cell recruitment. Recent evidence indicates that DENV infection induced MIF production and may contribute to vascular hyperpermeability and viral replication during DENV infection. The expression of both adhesion and coagulation molecules on MIF-stimulated monocytes and endothelial cells is also increased, which may contribute to inflammatory and anticoagulatory states during DHF/DSS. Therefore, blocking MIF production or its function may provide a solution for the treatment and prevention of DHF/DSS.

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Dengue Virus Infection Induced NF-κB-dependent Macrophage Migration Inhibitory Factor Production

Cited by 6 publications

References 18 publications

Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability

Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability

Roles of Macrophage Migration Inhibitory Factor in Dengue Pathogenesis: From Pathogenic Factor to Therapeutic Target

Pathogenic Roles of Macrophage Migration Inhibitory Factor during Dengue Virus Infection

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