Anti-inflammatory Effects of Variola Virus TNF Decoy Receptor in an Experimental Model of Contact Dermatitis

Elena A. Viazovaia; Irina P. Gileva; Ludmila B. Toporkova; Sergei N. Shchelkunov; Irina A. Orlovskaya

doi:10.2174/1389201019666181029111011

Anti-inflammatory Effects of Variola Virus TNF Decoy Receptor in an Experimental Model of Contact Dermatitis

Elena A. Viazovaia, Irina P. Gileva, Ludmila B. Toporkova, Sergei N. Shchelkunov, Irina A. Orlovskaya

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Large DNA poxviruses encode a diverse family of secreted proteins that modulate host inflammatory and antiviral responses, in particular by inhibiting one of the key players of the mammalian immune system, the tumor necrosis factor (TNF).

Methods: We investigated the effects of a recombinant variola (smallpox) virus TNF-decoy receptor (VARV-CrmB) in a murine model of contact dermatitis. Our results demonstrate that the VARV-CrmB protein significantly reduces the 2,4-dinitrochlorbenzene (DNCB)-induced migration of skin leukocytes during the sensitization phase and suppresses ear oedema during the elicitation phase of the contact reaction.

Results: Studies focusing on the bone marrow hematopoiesis in the contact dermatitis model revealed that the epicutaneous co-application of DNCB and VARV-CrmB protein normalized the DNCB-induced effects to control levels.

Conclusion: As an effective TNF antagonist, the VARV-CrmB protein might be conceived as a beneficial candidate for further research and development of therapeutic approaches in the field of the inflammatory skin diseases.

Original language	English
Pages (from-to)	910-916
Number of pages	7
Journal	Current Pharmaceutical Biotechnology
Volume	19
Issue number	11
DOIs	https://doi.org/10.2174/1389201019666181029111011
Publication status	Published - 1 Jan 2019

Keywords

Bone marrow
cell migration
contact dermatitis
hematopoiesis
human TNF (hTNF)
murine TNF (muTNF)
TNF-decoy receptor
variola virus
TUMOR-NECROSIS-FACTOR
LANGERHANS CELL-MIGRATION
FACTOR-ALPHA
BINDING PROTEINS
SKIN
SENSITIZATION
ANTAGONIST
INHIBITORS
INDUCTION
GENES
Variola virus
TNFdecoy receptor
Hematopoiesis
Human TNF (hTNF)
Murine TNF (muTNF)
Contact dermatitis
Cell migration
Tumor Necrosis Factor Decoy Receptors/isolation & purification
Viral Proteins/administration & dosage
Humans
Male
Tumor Necrosis Factor-alpha/antagonists & inhibitors
Anti-Inflammatory Agents/isolation & purification
Disease Models, Animal
Dinitrochlorobenzene/immunology
Animals
Receptors, Tumor Necrosis Factor/administration & dosage
Mice
Mice, Inbred BALB C
Haptens/immunology
Dermatitis, Allergic Contact/drug therapy

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10.2174/1389201019666181029111011

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title = "Anti-inflammatory Effects of Variola Virus TNF Decoy Receptor in an Experimental Model of Contact Dermatitis",

abstract = "Background: Large DNA poxviruses encode a diverse family of secreted proteins that modulate host inflammatory and antiviral responses, in particular by inhibiting one of the key players of the mammalian immune system, the tumor necrosis factor (TNF).Methods: We investigated the effects of a recombinant variola (smallpox) virus TNF-decoy receptor (VARV-CrmB) in a murine model of contact dermatitis. Our results demonstrate that the VARV-CrmB protein significantly reduces the 2,4-dinitrochlorbenzene (DNCB)-induced migration of skin leukocytes during the sensitization phase and suppresses ear oedema during the elicitation phase of the contact reaction.Results: Studies focusing on the bone marrow hematopoiesis in the contact dermatitis model revealed that the epicutaneous co-application of DNCB and VARV-CrmB protein normalized the DNCB-induced effects to control levels.Conclusion: As an effective TNF antagonist, the VARV-CrmB protein might be conceived as a beneficial candidate for further research and development of therapeutic approaches in the field of the inflammatory skin diseases.",

keywords = "Bone marrow, cell migration, contact dermatitis, hematopoiesis, human TNF (hTNF), murine TNF (muTNF), TNF-decoy receptor, variola virus, TUMOR-NECROSIS-FACTOR, LANGERHANS CELL-MIGRATION, FACTOR-ALPHA, BINDING PROTEINS, SKIN, SENSITIZATION, ANTAGONIST, INHIBITORS, INDUCTION, GENES, Variola virus, TNFdecoy receptor, Hematopoiesis, Human TNF (hTNF), Murine TNF (muTNF), Contact dermatitis, Cell migration, Tumor Necrosis Factor Decoy Receptors/isolation & purification, Viral Proteins/administration & dosage, Humans, Male, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Anti-Inflammatory Agents/isolation & purification, Disease Models, Animal, Dinitrochlorobenzene/immunology, Animals, Receptors, Tumor Necrosis Factor/administration & dosage, Mice, Mice, Inbred BALB C, Haptens/immunology, Dermatitis, Allergic Contact/drug therapy",

author = "Viazovaia, {Elena A.} and Gileva, {Irina P.} and Toporkova, {Ludmila B.} and Shchelkunov, {Sergei N.} and Orlovskaya, {Irina A.}",

note = "Copyright{\textcopyright} Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.",

year = "2019",

month = jan,

day = "1",

doi = "10.2174/1389201019666181029111011",

language = "English",

volume = "19",

pages = "910--916",

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issn = "1389-2010",

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TY - JOUR

T1 - Anti-inflammatory Effects of Variola Virus TNF Decoy Receptor in an Experimental Model of Contact Dermatitis

AU - Viazovaia, Elena A.

AU - Gileva, Irina P.

AU - Toporkova, Ludmila B.

AU - Shchelkunov, Sergei N.

AU - Orlovskaya, Irina A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Large DNA poxviruses encode a diverse family of secreted proteins that modulate host inflammatory and antiviral responses, in particular by inhibiting one of the key players of the mammalian immune system, the tumor necrosis factor (TNF).Methods: We investigated the effects of a recombinant variola (smallpox) virus TNF-decoy receptor (VARV-CrmB) in a murine model of contact dermatitis. Our results demonstrate that the VARV-CrmB protein significantly reduces the 2,4-dinitrochlorbenzene (DNCB)-induced migration of skin leukocytes during the sensitization phase and suppresses ear oedema during the elicitation phase of the contact reaction.Results: Studies focusing on the bone marrow hematopoiesis in the contact dermatitis model revealed that the epicutaneous co-application of DNCB and VARV-CrmB protein normalized the DNCB-induced effects to control levels.Conclusion: As an effective TNF antagonist, the VARV-CrmB protein might be conceived as a beneficial candidate for further research and development of therapeutic approaches in the field of the inflammatory skin diseases.

AB - Background: Large DNA poxviruses encode a diverse family of secreted proteins that modulate host inflammatory and antiviral responses, in particular by inhibiting one of the key players of the mammalian immune system, the tumor necrosis factor (TNF).Methods: We investigated the effects of a recombinant variola (smallpox) virus TNF-decoy receptor (VARV-CrmB) in a murine model of contact dermatitis. Our results demonstrate that the VARV-CrmB protein significantly reduces the 2,4-dinitrochlorbenzene (DNCB)-induced migration of skin leukocytes during the sensitization phase and suppresses ear oedema during the elicitation phase of the contact reaction.Results: Studies focusing on the bone marrow hematopoiesis in the contact dermatitis model revealed that the epicutaneous co-application of DNCB and VARV-CrmB protein normalized the DNCB-induced effects to control levels.Conclusion: As an effective TNF antagonist, the VARV-CrmB protein might be conceived as a beneficial candidate for further research and development of therapeutic approaches in the field of the inflammatory skin diseases.

KW - Bone marrow

KW - cell migration

KW - contact dermatitis

KW - hematopoiesis

KW - human TNF (hTNF)

KW - murine TNF (muTNF)

KW - TNF-decoy receptor

KW - variola virus

KW - TUMOR-NECROSIS-FACTOR

KW - LANGERHANS CELL-MIGRATION

KW - FACTOR-ALPHA

KW - BINDING PROTEINS

KW - SKIN

KW - SENSITIZATION

KW - ANTAGONIST

KW - INHIBITORS

KW - INDUCTION

KW - GENES

KW - Variola virus

KW - TNFdecoy receptor

KW - Hematopoiesis

KW - Human TNF (hTNF)

KW - Murine TNF (muTNF)

KW - Contact dermatitis

KW - Cell migration

KW - Tumor Necrosis Factor Decoy Receptors/isolation & purification

KW - Viral Proteins/administration & dosage

KW - Humans

KW - Male

KW - Tumor Necrosis Factor-alpha/antagonists & inhibitors

KW - Anti-Inflammatory Agents/isolation & purification

KW - Disease Models, Animal

KW - Dinitrochlorobenzene/immunology

KW - Animals

KW - Receptors, Tumor Necrosis Factor/administration & dosage

KW - Mice

KW - Mice, Inbred BALB C

KW - Haptens/immunology

KW - Dermatitis, Allergic Contact/drug therapy

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U2 - 10.2174/1389201019666181029111011

DO - 10.2174/1389201019666181029111011

M3 - Article

C2 - 30370844

VL - 19

SP - 910

EP - 916

JO - Current Pharmaceutical Biotechnology

JF - Current Pharmaceutical Biotechnology

SN - 1389-2010

IS - 11

ER -

Anti-inflammatory Effects of Variola Virus TNF Decoy Receptor in an Experimental Model of Contact Dermatitis

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Keywords

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