Differential modulation of hepatitis C virus replication and innate immune pathways by synthetic calcitriol-analogs

Saleh, Maged; Welsch, Christoph; Cai, Chengcong; Döring, Claudia; Gouttenoire, Jérôme; Friedrich, J; Haselow, Katrin; Sarrazin, Christoph; Badenhoop, Klaus; Moradpour, Darius; Zeuzem, Stefan; Rueschenbaum, Sabrina; Lange, Christian

doi:10.1016/j.jsbmb.2018.06.008

Cited by 12 publications

(10 citation statements)

References 45 publications

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“…On the contrary, synthetic calcitriol derived calcipotriol had been shown to inhibit HCV replication by inducing vitamin D receptor target genes like cathelicidin and hepcidin. However, the underlying mechanism of inhibiting HCV replication by calcipotriol remains unknown [97].…”

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections

et al. 2020

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Antimicrobial peptides (AMPs) are produced by neutrophils, monocytes, and macrophages, as well as epithelial cells, and are an essential component of innate immunity system against infection, including several viral infections. AMPs, in particular the cathelicidin LL-37, also exert numerous immunomodulatory activities by inducing cytokine production and attracting and regulating the activity of immune cells. AMPs are scarcely expressed in normal skin, but their expression increases when skin is injured by external factors, such as trauma, inflammation, or infection. LL-37 complexed to self-DNA acts as autoantigen in psoriasis and lupus erythematosus (LE), where it also induces production of interferon by plasmocytoid dendritic cells and thus initiates a cascade of autocrine and paracrine processes, leading to a disease state. In these disorders, epidermal keratinocytes express high amounts of AMPs, which can lead to uncontrolled inflammation. Similarly, LL-37 had several favorable and unfavorable roles in virus replication and disease pathogenesis. Targeting the antiviral and immunomodulatory functions of LL-37 opens a new approach to limit virus dissemination and the progression of disease.

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Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections

et al. 2020

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“…Gutierrez et al and Lin et al reported the anti-HCV replication activities of VD derivatives including VD 2 , VD 3 , and 1,25(OH) 2 D 3 at 1-5 µM concentrations in vitro [27,28]. Structurally related VD analogs, such as calcipotriol and tacalcitol, also suppressed HCV replication in vitro [29]. Mechanistically, the activation of the interferon (IFN) signaling pathway, the blockade of peroxisome proliferator-activated receptor (PPAR), and the inhibition of endoplasmic reticulum-associated degradation (ERAD) pathways by VD were proposed as their modes of action [23,28].…”

Section: Effect Of Vd On Hcv Infectionmentioning

confidence: 98%

Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes

Lee

2020

Nutrients

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Vitamin D (VD) plays an essential role in mineral homeostasis and bone remodeling. A number of different VD-related genes (VDRG) are required for the metabolic activation of VD and the subsequent induction of its target genes. They include a set of genes that encode for VD-binding protein, metabolic enzymes, and the VD receptor. In addition to its well-characterized skeletal function, the immunoregulatory activities of VD and the related polymorphisms of VDRG have been reported and linked to its therapeutic and preventive actions for the control of several viral diseases. However, in regards to their roles in the progression of viral diseases, inconsistent and, in some cases, contradictory results also exist. To resolve this discrepancy, I conducted an extensive literature search by using relevant keywords on the PubMed website. Based on the volume of hit papers related to a certain viral infection, I summarized and compared the effects of VD and VDRG polymorphism on the infection, pathogenesis, and treatment outcomes of clinically important viral diseases. They include viral hepatitis, respiratory viral infections, acquired immunodeficiency syndrome (AIDS), and other viral diseases, which are caused by herpesviruses, dengue virus, rotavirus, and human papillomavirus. This review will provide the most current information on the nutritional and clinical utilization of VD and VDRG in the management of the key viral diseases. This information should be valuable not only to nutritionists but also to clinicians who wish to provide evidence-based recommendations on the use of VD to virally infected patients.

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“…The inhibition of HCV replication by vitamin D derivatives, including vitamin D2, vitamin D3, and 1,25(OH)2D3, was observed in vitro [ 72 , 77 ]. Saleh et al [ 78 ] investigated the mechanism of selected calcitriol analogs in regulating the hepatocellular transcriptome and suppressing HCV, and reported that the structurally related vitamin D analogs calcipotriol and tacalcitiol, but not calcitriol itself, inhibited HCV replication via a VDR-dependent pathway. Specifically, critical regulatory elements of the VDR bind to calcipotriol through distinct local interaction patterns that affect key functional residues and elicit stronger regulatory effects on the hepatocyte and macrophage transcriptome [ 78 ].…”

Section: Possible Mechanisms Of the Association Between Vitamin D–vdr...mentioning

confidence: 99%

Vitamin D–VDR Novel Anti-Inflammatory Molecules—New Insights into Their Effects on Liver Diseases

Αγγελετοπούλου

Thomopoulos

Mouzaki

et al. 2022

IJMS

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There is consistent evidence that vitamin D deficiency is strongly associated with liver dysfunction, disease severity, and poor prognosis in patients with liver disease. Vitamin D and its receptor (VDR) contribute to the regulation of innate and adaptive immune responses. The presence of genetic variants of vitamin D- and VDR-associated genes has been associated with liver disease progression. In our recent work, we summarized the progress in understanding the molecular mechanisms involved in vitamin D–VDR signaling and discussed the functional significance of VDR signaling in specific cell populations in liver disease. The current review focuses on the complex interaction between immune and liver cells in the maintenance of liver homeostasis and the development of liver injury, the interplay of vitamin D and VDR in the development and outcome of liver disease, the role of vitamin D- and VDR-associated genetic variants in modulating the occurrence and severity of liver disease, and the therapeutic value of vitamin D supplementation in various liver diseases. The association of the vitamin D–VDR complex with liver dysfunction shows great potential for clinical application and supports its use as a prognostic index and diagnostic tool.

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Differential modulation of hepatitis C virus replication and innate immune pathways by synthetic calcitriol-analogs

Cited by 12 publications

References 45 publications

Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections

Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections

Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes

Vitamin D–VDR Novel Anti-Inflammatory Molecules—New Insights into Their Effects on Liver Diseases

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